动物造模 z-bio 2022-11-29 470

　　OBJECTIVE: To study the differences in the degree of suppression of adrenal cortex function and the induction of drug-induced syndromes after glucocorticoids act on different strains of mice.

　　Methods: Five kinds of mice, ICR, BALB/c, C57BL/6J, KM and nude mice were selected as experimental objects, and prednisolone was used for intervention. There were 16 mice in each type, including 8 in normal control group and 8 in prednisolone. There were 8 mice in the Solomon group. Prednisolone was given 0.5 mg/(kg·d) by gavage for 14 days, and the body weight of the mice was observed every day. The next day, the mice were sacrificed, the spleen and thymus were weighed and the organ index was calculated; serum corticosterone and ACTH levels were detected by ELISA; adrenal Star, Cyp11a1, Cyp21a1, Cyp11b1, Cyp11b2 gene expression was detected by real-time fluorescence quantitative PCR technology. ;Adrenal LDLR, SRBI, StAR protein expressions were detected by Western blot.

　　Results: Compared with the respective control groups: 1) The body weight of ICR mice decreased significantly from the 7th day after administration of 0.5mg/(kg·d) prednisolone (P<0.01); from the 13th day after administration, BALB/(kg·d) The body weight of c mice decreased significantly (P<0.01); the body weight of C57BL/6J mice decreased significantly from the 5th day after administration (P<0.01); the body weight of nude mice decreased significantly on the 13th day after administration (P<0.05). 2) Prednisolone resulted in a significant decrease in grip strength and a significant decrease in average trunk temperature in ICR mice (P<0.05). 3) Prednisolone resulted in a significant decrease in spleen weight in ICR mice and nude mice (P<0.01) as well as in nude mice (P<0.05). The spleen index of mice decreased (P<0.05), and prednisolone significantly decreased the thymus weight and thymus index of ICR, C57BL/6J and KM mice (P<0.01). Serum corticosterone in KM mice decreased (P<0.05), and also significantly decreased serum adrenocorticotropic hormone (ACTH) levels in BALB/c mice (P<0.01). 5) Prednisolone significantly down-regulated adrenal Cyp21a1 in ICR mice Gene expression (P<0.05), down-regulated the expression of Star gene in C57BL/6J mice (P<0.01), down-regulated the gene expression of Cyp11a1 and Cyp21a1 in KM mice (P<0.01), down-regulated the gene expression of Star and Cyp21a1 in nude mice (P<0.05) ); and prednisolone inhibited adrenal LDLR protein expression in ICR mice and adrenal StAR protein expression in KM mice.

　　Conclusion: The drug-induced deficiency syndrome caused by prednisolone in mice is mainly manifested as "Qi deficiency", which involves "kidney storage" and "spleen storage" in traditional Chinese medicine, and its material basis is the inhibition of the expression of adrenocorticosteroid synthase molecules and pituitary-adrenal axis function is mainly inhibited; it is recommended that ICR mice be the first choice for research on drug-induced deficiency of glucocorticoids.