动物造模,胰腺炎 z-bo 2022-02-02 417

Caerulein is an analog of cholecystokinin (CCK). Cholecystokinin is a polypeptide hormone composed of 33 amino acids. Its main physiological function is to stimulate the contraction of the gallbladder and the relaxation of the Oddi sphincter, promote the secretion of liver and bile, regulate the movement of the small intestine and colon, stimulate the exocrine secretion of the pancreas, and regulate food intake.

[Modeling mechanism] Overdose of ceruloplasmin mediated by CCK receptor stimulates excessive secretion of pancreatic acinar cells and activates the cathepsin B-dependent intracellular separation of trypsinogen and lysosomal hydrolase. The activity further leads to the activation of the zymogen, which leads to a series of cell damage caused by the protease activity. The inflammatory response caused by autolysis of pancreatic tissue recruits inflammatory cells, releases inflammatory factors, and even causes severe local or systemic inflammation. The cause of acute pancreatitis is relatively clear and can mimic the outbreak of human disease. However, the cause of chronic pancreatitis is still unknown. Repeated acute pancreatitis causes chronic pancreatitis, and repeated acute pancreatitis causes pathological features of chronic pancreatitis, such as pancreatic fibrosis and chronic pancreatitis. .. Basic modeling mechanism. When cyanobacteria induce pancreatitis, it is often combined with factors that are sensitive to pancreatitis, such as endotoxin, ethanol, and hypertriglyceridemia. Lipopolysaccharide (LPS) is an endotoxin that activates monocytes and releases cytokines that cause systemic inflammation. Clinical studies have found that LPS levels are closely related to the severity of acute pancreatitis. The combination of cerulein and LPS has a synergistic effect in establishing pancreatitis models. LPS destroys the normal response of inflammatory mediators, develops into local pancreatitis, becomes a systemic and severe inflammatory response, and aggravates pancreatitis due to the induction of cerulein. Ethanol will increase the oxidative stress of the pancreas, destroy the mitochondria in the acinar cells, promote the activation of trypsinogen, change the neuroendocrine regulation, and transform cell death from apoptosis to necrosis through the anti-inflammatory response to promote pancreatic fibrosis. Therefore, whether to prepare acute or chronic pancreatitis models, the application of ethanol may promote pancreatitis caused by other methods. Hypertriglyceridemia is an important cause of acute pancreatitis, but its mechanism is unclear. In the hypertriglyceridemia model, penicillin-induced pancreatitis has been shown to aggravate the severity of pancreatitis, but only severe hypertriglyceridemia (1000mg/dl) model has been observed. There are very few models of this type. Only hamsters cause severe hypertriglyceridemia through eating, lipoprotein lipase and its cofactor GPIHBP1 knockout mice and its inhibitor ApoC3 transgenic mice with severe hypertriglyceridemia phenotype may become ill. In addition, GPIHBP1 knockout rats have recently been successfully prepared, and given the advantages of rats in acute pancreatitis research, it may be the best tool for the treatment of acute pancreatitis in the future. These models can be used to study acute hypertriglyceridemia and acute pancreatitis. Dibutyltin dichloride (DBTC) and other dialkyl tins cause bile duct epithelial cell destruction, edema and proliferation, pancreaticobiliary duct obstruction, the formation of acute interstitial pancreatitis, and pancreatic fibrosis due to chronic inflammation.. DBTC is usually associated with Used in combination with cerulein, cerulein is a more typical model of chronic pancreatitis. [Modeling method] In theory, aeruginin induces acute pancreatitis in most animals, but such models are mainly used in rodents (rats, mice, etc.). Rats are injected with 5-20μg/kg body weight every hour or orally subcutaneously for 4-6 hours, and 20-50μg/kg body weight mice are injected intraperitoneally every hour. Although hamsters are not a commonly used model of acute pancreatitis due to their significant advantages in lipid pancreas, studies have shown that they are equally sensitive to acute pancreatitis induced by the rat or mouse method. I found. Cerulein-induced chronic pancreatitis is the basic method to create this model. In any type of animal, when acute pancreatitis is induced many times, once a week for several weeks or even longer, more typical pathological symptoms of chronic pancreatitis will appear. Mice are also the most commonly used animals in chronic pancreatitis models. This is because transgenic mice are the main research tool for the relationship between chronic pancreatitis and individual genes. When LPS is used in combination with cerulein to induce acute pancreatitis, usually 5-15 mg/kg is injected intraperitoneally and added after the last injection of cerulein. According to reports, combining ceruloplasmin with LPS can reduce a single injection of ceruloplasmin. Ethanol can be used alone or in combination with microlanin to induce acute and chronic pancreatitis. Ethanol can be given in large doses by gavage. If the experiment is performed in mice, 100 μl of 50% to 60% ethanol can be administered 4 times a day, or 20% ethanol can be administered 10 times a day. Acute pancreatitis was not induced in wild mice, nor did it aggravate penicillin-induced acute pancreatitis. Long-term use of ethanol is a common method for preparing chronic pancreatitis. The most reliable way to administer ethanol is the Lieber-DeCarli diet. This allows animals to receive adequate amounts of ethanol and nutrients for a long time, thereby effectively eliminating malnutrition caused by long-term ethanol intake. The Decali lever is equivalent to the liquid diet containing all nutrients and ethanol proposed in 1963. The calorie formula is 18% protein and 21% fat. , 47% carbohydrates (36% of calories are replaced by ethanol) and some vitamins and inorganic salts. Usually, after taking ethanol for 10 weeks, LPS (3mg/kg) is increased once a week for 3 consecutive weeks, causing chronic pancreatitis.

　　The combination of cerulein and DBTC can prevent chronic pancreatitis and is more commonly used in rats. DBTC was dissolved in 100% ethanol, diluted with glycerol, and injected into the tail vein at a dose of 4.5 mg/kg body weight once. DBTC combined with ethanol can also be used to prepare chronic pancreatitis models.

　　[Characteristics of the model] After the injection of ceruloplasmin, the peak values of animal plasma amylase and lipase increased from dozens of times to thousands of times. This may be related to drug dosage and various laboratory methods. It is usually found in pathological sections of pancreatic tissue. There is a small amount of necrosis of the pancreas, inflammatory cell infiltration, sometimes bleeding, and round vacuoles. The expression level of inflammatory factors in serum and pancreatic tissue increased. In this type of model, the pathological mechanism of pancreatitis is different, and the animal's apoptosis and autophagy are also different. Animal models of cervicin-induced pancreatitis may also show typical acute pancreatitis-related lung damage, especially when used in combination with LPS. Pathological characteristics of chronic pancreatitis model

　　Caerulein is an analog of cholecystokinin (CCK). Cholecystokinin is a polypeptide hormone composed of 33 amino acids. Its main physiological function is to stimulate the contraction of the gallbladder and the relaxation of the Oddi sphincter, promote the secretion of liver and bile, regulate the movement of the small intestine and colon, stimulate the exocrine secretion of the pancreas, and regulate food intake. It functions as a hormone.

[Modeling mechanism] Overdose of ceruloplasmin mediated by CCK receptor stimulates excessive secretion of pancreatic acinar cells and activates the cathepsin B-dependent intracellular separation of trypsinogen and lysosomal hydrolase. The activity further leads to the activation of the zymogen, which leads to a series of cell damage caused by the protease activity. The inflammatory response caused by autolysis of pancreatic tissue recruits inflammatory cells, releases inflammatory factors, and even causes severe local or systemic inflammation. The cause of acute pancreatitis is relatively clear and can mimic the outbreak of human disease. However, the cause of chronic pancreatitis is still unknown. Repeated acute pancreatitis causes chronic pancreatitis, and repeated acute pancreatitis causes pathological features of chronic pancreatitis, such as pancreatic fibrosis and chronic pancreatitis. .. Basic modeling mechanism. When cyanobacteria induce pancreatitis, it is often combined with factors that are sensitive to pancreatitis, such as endotoxin, ethanol, and hypertriglyceridemia. Lipopolysaccharide (LPS) is an endotoxin that activates monocytes and releases cytokines that cause systemic inflammation. Clinical studies have found that LPS levels are closely related to the severity of acute pancreatitis. The combination of cerulein and LPS has a synergistic effect in establishing pancreatitis models. LPS destroys the normal response of inflammatory mediators, develops into local pancreatitis, becomes a systemic and severe inflammatory response, and aggravates pancreatitis due to the induction of cerulein. Ethanol will increase the oxidative stress of the pancreas, destroy the mitochondria in the acinar cells, promote the activation of trypsinogen, change the neuroendocrine regulation, and transform cell death from apoptosis to necrosis through the anti-inflammatory response to promote pancreatic fibrosis. Therefore, whether to prepare acute or chronic pancreatitis models, the application of ethanol may promote pancreatitis caused by other methods. Hypertriglyceridemia is an important cause of acute pancreatitis, but its mechanism is unclear. In the hypertriglyceridemia model, penicillin-induced pancreatitis has been shown to aggravate the severity of pancreatitis, but only severe hypertriglyceridemia (1000mg/dl) model has been observed. There are very few models of this type. Only hamsters cause severe hypertriglyceridemia through eating, lipoprotein lipase and its cofactor GPIHBP1 knockout mice and its inhibitor ApoC3 transgenic mice with severe hypertriglyceridemia phenotype may become ill. In addition, GPIHBP1 knockout rats have recently been successfully prepared, and given the advantages of rats in acute pancreatitis research, it may be the best tool for the treatment of acute pancreatitis in the future. These models can be used to study acute hypertriglyceridemia and acute pancreatitis. Dibutyltin dichloride (DBTC) and other dialkyl tins cause bile duct epithelial cell destruction, edema and proliferation, pancreaticobiliary duct obstruction, the formation of acute interstitial pancreatitis, and pancreatic fibrosis due to chronic inflammation.. DBTC is usually associated with Used in combination with cerulein, cerulein is a more typical model of chronic pancreatitis. [Modeling method] In theory, aeruginin induces acute pancreatitis in most animals, but such models are mainly used in rodents (rats, mice, etc.). Rats are injected with 5-20μg/kg body weight every hour or orally subcutaneously for 4-6 hours, and 20-50μg/kg body weight mice are injected intraperitoneally every hour. Although hamsters are not a commonly used model of acute pancreatitis due to their significant advantages in lipid pancreas, studies have shown that they are equally sensitive to acute pancreatitis induced by the rat or mouse method. I found. Cerulein-induced chronic pancreatitis is the basic method to create this model. In any type of animal, when acute pancreatitis is induced many times, once a week for several weeks or even longer, more typical pathological symptoms of chronic pancreatitis will appear. Mice are also the most commonly used animals in chronic pancreatitis models. This is because transgenic mice are the main research tool for the relationship between chronic pancreatitis and individual genes. When LPS is used in combination with cerulein to induce acute pancreatitis, usually 5-15 mg/kg is injected intraperitoneally and added after the last injection of cerulein. According to reports, combining ceruloplasmin with LPS can reduce a single injection of ceruloplasmin. Ethanol can be used alone or in combination with microlanin to induce acute and chronic pancreatitis. Ethanol can be given in large doses by gavage. If the experiment is performed in mice, 100 μl of 50% to 60% ethanol can be administered 4 times a day, or 20% ethanol can be administered 10 times a day. Acute pancreatitis was not induced in wild mice, nor did it aggravate penicillin-induced acute pancreatitis. Long-term use of ethanol is a common method for preparing chronic pancreatitis. The most reliable way to administer ethanol is the Lieber-DeCarli diet. This allows animals to receive adequate amounts of ethanol and nutrients for a long time, thereby effectively eliminating malnutrition caused by long-term ethanol intake. The Decali lever is equivalent to the liquid diet containing all nutrients and ethanol proposed in 1963. The calorie formula is 18% protein and 21% fat. , 47% carbohydrates (36% of calories are replaced by ethanol) and some vitamins and inorganic salts. Usually, after taking ethanol for 10 weeks, LPS (3mg/kg) is increased once a week for 3 consecutive weeks, causing chronic pancreatitis.

　　The combination of cerulein and DBTC can prevent chronic pancreatitis and is more commonly used in rats. DBTC was dissolved in 100% ethanol, diluted with glycerol, and injected into the tail vein at a dose of 4.5 mg/kg body weight once. DBTC combined with ethanol can also be used to prepare chronic pancreatitis models.

　　[Characteristics of the model] After the injection of ceruloplasmin, the peak values of animal plasma amylase and lipase increased from dozens of times to thousands of times. This may be related to drug dosage and various laboratory methods. It is usually found in pathological sections of pancreatic tissue. There is a small amount of necrosis of the pancreas, inflammatory cell infiltration, sometimes bleeding, and round vacuoles. The expression level of inflammatory factors in serum and pancreatic tissue increased. In this type of model, the pathological mechanism of pancreatitis is different, and the animal's apoptosis and autophagy are also different. Animal models of cervicin-induced pancreatitis may also show typical acute pancreatitis-related lung damage, especially when used in combination with LPS. The pathological features of the chronic pancreatitis model include loss of exocrine and endocrine cells, typical chronic inflammation, formation of protein embolism and calcification in the duct, pain sensitivity, and pancreatic fibrosis.

　　[Evaluation and application of the model] Ceratophyll-induced acute pancreatitis is the most commonly used method for pancreatitis modeling because of its easy operation, short experimental period and good repeatability. This type of model is suitable for studying the cellular biological mechanism of acute pancreatitis and plays an important role in the study of genetic and environmental factors of the etiology. The reported species are rats, mice, dogs, rabbits and gophers. The cerulein analog CCK can be used for in vitro experimental research and can simulate the in vivo experimental mechanism of cerulein, which is very useful for cell biology research. Since ceruloplasmin can induce mild to moderate acute pancreatitis and can heal itself, it is used for early cell mechanism research and repair of acinar cell damage to observe the effects of new prevention and treatment methods. Good for. However, when evaluating prevention and treatment methods, amylase and lipase are not sensitive indicators, and biochemical indicators rely on the measurement of inflammatory factors. No one. This model requires large but not low-cost injections of ceruloplasmin, induces self-limiting acute pancreatitis, and is relatively insensitive to mice. Compare the sensitivity of different strains of mice to penicillin-induced pancreatitis. C57BL/6 mice are less sensitive, while BALB/c and ICR mice are more sensitive. In the course of pancreatitis of the same strain, the pancreatitis induced by cerebellin is slightly different. Therefore, when applying this type of model, an appropriate control group and observations over time are needed. Moreover, the model cannot simulate the common causes of human diseases, and there is no end to death. Often other interventional and severe models of pancreatitis are needed as supplementary models for research. The injection of ceruloplasmin while providing LPS stimulation supplements the limitations of using ceruloplasmin in the model to a certain extent.

"Signs" include loss of exocrine and endocrine cells, typical chronic inflammation, formation of protein embolism and calcification in ducts, pain sensitivity and pancreatic fibrosis. [Evaluation and application of the model] Acute pancreatitis induced by cervicin is the most commonly used method for modeling pancreatitis because of its easy operation, short experimental period and good repeatability. This type of model is suitable for studying the cellular biological mechanism of acute pancreatitis and plays an important role in the study of genetic and environmental factors of the etiology. The reported species are rats, mice, dogs, rabbits and gophers. The cerulein analog CCK can be used for in vitro experimental research and can simulate the in vivo experimental mechanism of cerulein, which is very useful for cell biology research. Since ceruloplasmin can induce mild to moderate acute pancreatitis and can heal itself, it is used for early cell mechanism research and repair of acinar cell damage to observe the effects of new prevention and treatment methods. Good for. However, when evaluating prevention and treatment methods, amylase and lipase are not sensitive indicators, and biochemical indicators rely on the measurement of inflammatory factors. No one. This model requires large but not low-cost injections of ceruloplasmin, induces self-limiting acute pancreatitis, and is relatively insensitive to mice. Compare the sensitivity of different strains of mice to penicillin-induced pancreatitis. C57BL/6 mice are less sensitive, while BALB/c and ICR mice are more sensitive. In the course of pancreatitis of the same strain, the pancreatitis induced by cerebellin is slightly different. Therefore, when applying this type of model, an appropriate control group and observations over time are needed. Moreover, the model cannot simulate the common causes of human diseases, and there is no end to death. Often other interventional and severe models of pancreatitis are needed as supplementary models for research. The injection of ceruloplasmin while providing LPS stimulation supplements the limitations of using ceruloplasmin in the model to a certain extent.