先天性室间隔缺损,动物造模 z-bo 2022-02-19 512

　　The incidence of congenital ventricular septal defect (VSD) in infants born in humans is about 0.1% to 0.2%, and it is one of the most common congenital malformations. The severity of VSD varies greatly and can lead to death or chronic left ventricular to right ventricular ejection shunt-related diseases. Severe shunt (Qp: Qs>1.5: 1.0,) requires surgical correction. VSD may also be related to other heart malformations, such as Tetralogy of Fallot. The various symptoms of VSD are related to genetic factors and environmental factors.

　　Many animal species have reported cases of VSD, but only chickens, dogs and Yucatan minipigs have VSDs that have been studied in detail according to human disease models. VSD has been reported in domestic pigs, but it is not a renewable model. Yucatan small pigs have developed a reproducible genetic VSD model and can provide commercial models for experimental research applications.

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　　VSD model is derived from an accidental discovery in a commercial breeding population of Yucatan miniature pigs. A retrospective analysis of the basic blood population found that all diseased animals originated from a single breeding boar. A retrospective analysis of the basic population of animals found that the incidence of VSD has nothing to do with gender, and the affected offspring will increase with the degree of association and inbreeding. The average inbreeding coefficient of diseased animals is 0.042, while that of normal animals is 0.025. The correlation degree between the sick offspring and their grandparents is 0.0757, and the correlation degree between the normal offspring and their grandparents is 0.037.

　　Based on the pedigree analysis of the parent population, scholars conducted a series of experimental breeding studies on the experimental group established by the Medical University of South Carolina in 1987. Experimental breeding includes: unrelated individuals, brothers and sisters, parents and their offspring. The results of the study showed that, like the parent population, no correlation between sex and the incidence of VSD was observed. The occurrence of VSD is not an autosomal dominant inheritance, because not all the offspring of diseased animals have the disease, and the defect can be transmitted by the mating of animals without disease. However, the possibility of incomplete penetrance cannot be completely ruled out. The occurrence of VSD is also not classified as autosomal recessive inheritance, because in the test mating, the incidence of offspring is too high, and the incidence of parents, siblings, offspring and closely related individuals is also high. Using Mendelian genetic theory to analyze and confirm that multi-gene or multi-factor inheritance is the most likely inheritance mode of VSD.

　　In order to further clarify the genetic pattern of VSD in this group of animals, an attempt was made to establish an inbred line, but due to infertility in the fifth generation of inbred animals, the study could not be continued. The current commercial VSD model miniature pigs are provided through selective breeding methods, because the degree of association and inbreeding are related to the incidence of VSD. Through selective breeding in the parent population, pregnant sows and more In the offspring of diseased piglets, this method has a high success rate in obtaining diseased animals.

　　VSD in Yucatan minipigs can be detected by auscultation. Diseased animals can hear heart murmurs between the systolic period or the entire systolic period between the third to fifth ribs of the lower edge of any side of the thorax. Most VSD minipigs do not show clinical symptoms, and a small number of animals will experience sudden death, dysplasia, pulmonary hypertension, or VSD-related heart failure. This may be related to the pig's less active lifestyle, if exercise testing can accelerate the appearance of symptoms. If heart failure occurs in newborn piglets and piglets, it is generally not easy to find, and it usually shows significant symptoms when acute respiratory failure secondary to pulmonary edema. Because Yucatan minipigs have a dark skin color, it is difficult to identify clinical cyanosis caused by breathing difficulties. If breathing difficulties are found, parenteral administration of 10 mg/kg furosemide and supportive care are usually effective in relieving symptoms. Small VSD defects usually repair naturally as the animal matures.

　　Using cardiac catheterization technology and cardiovascular angiography, a clear diagnosis can be made for piglets, piglets and adult pigs. For animals with functional VSD, the shunt from left to right ventricle can be detected by blood oxygen saturation test. In experimental studies, shunts reaching 1.5:1.0 (Qp: Qs) or further magnification are considered to be significant changes in hemodynamics. An angiographic image can be obtained by selectively inserting a ventricular pigtail catheter, injecting contrast agent through an automatic injection device, and recording 60 frames per second.

　　In terms of hemodynamics, the VSD of pigs is similar to that of humans, but the clinical symptoms are not significant enough, except that the animals are under severe stress conditions, usually during transportation or some treatments that require anesthesia. For adult pigs, death during anesthesia is the most common; for young pigs and piglets, acute dyspnea is the most common clinical symptom. Pups suffering from dysplasia syndrome weigh 2 times the standard deviation lower than the average of piglets of the same age. The hemodynamic changes of these animals are more pronounced than other types of pigs, and the pathogenesis of human dysplasia syndrome patients is similar. Pulmonary hypertension is one of the earliest obvious hemodynamic abnormal changes caused by the obvious shunt of VSD, which mainly appears in dysplasia syndrome and animals over 12 months of age.

　　In short, VSD is one of the most common congenital heart malformations in humans. The most common defect in humans and pigs is the shunt from the left ventricle to the right ventricle. The anatomy is membranous, muscle, and double-involved or proximal to the artery. Concomitant membrane defects have a central fibrous body as part of their edges; muscle defects have muscle encircling defects and double involvement; proximal arterial defects have fibrous connections between the aortic and pulmonary valves and their outlets. All Yucatan minipig models are mainly located in the high position of the left ventricular aortic valve outlet duct. This model is widely used in basic and applied research on the pathogenesis of VSD and potential treatment methods. Yucatan minipigs provide a model with predictable VSD location and reliable regeneration through genetic selection techniques.