| Purpose:To observe the effects of Qidigushen formula on urinary protein,serum biochemical indexes,renal pathology and P53/PHB expression in rats with idiopathic membranous nephropathy(IMN),and explore the effect mechanism of Qidigushen formula on IMN.Method:1.The rat model of passive heymann nephritis(PHN)was established with rabbit antirat Fx1 A serum.2.They were divided into model group,Benazepril hydrochloride tablet group,Qidigushenfang low-dose group,Qidigushenfang medium-dose group,Qidigushenfang high-dose group,and blank group.The corresponding dose of drugs was given by intragastric administration for 4 weeks.3.The quantitative measurement of proteinuria at 24 hours and the levels of serum total protein(TP),albumin(ALB),cholesterol(TC),triglyceride(TG),urea nitrogen(BUN),creatinine(Scr),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)after administration were dynamically observed.The pathological changes of kidney were observed by PAS,MASSON staining and electron microscope.The expression levels of P53,PHB1,PHB2,apoptotic markers PARP and cleaved PARP in renal tissues were detected by Western Blot and RT-PCR.Results:1.Kidney protection effect of Qidi Gushen formula on IMN rats(1)Quantitative comparison of urinary protein at 24h: Compared with blank group,urinary protein in model group was significantly increased(P<0.01).Compared with model group,after 2 weeks of administration,the urinary protein level of each administration group decreased,but there was no statistical significance compared with model group(P>0.05).After 4 weeks of administration,urinary protein in medium and high dose groups and benazepril groups was significantly decreased(P<0.01).(2)Comparison of liver function,lipid and renal function indexes: Compared with blank group,serum TP and ALB levels in model group were decreased(P<0.01),while TC and TG levels were increased(P<0.01).Compared with model group,TP and ALB in medium and high dose groups and Benazepril groups were significantly increased(P <0.01);TC in medium and high dose groups and Benazepril group was significantly decreased(P<0.01),TG in low,medium and high dose groups and Benazepril group was significantly decreased(P<0.01);The levels of ALT,AST,Scr and BUN were not statistically significant among all groups.(3)Comparison of pathological injury of kidney: Compared with blank group,pathological injury of kidney in model group was significantly increased;Compared with the model group,Qidigushenfang low,medium and high dose groups and Benazepril group had different degrees of improvement in renal pathological morphology,the deposition of renal immune complex was reduced,the fusion rate of foot process was reduced,and the deposition of glomerular basement membrane was reduced.Among them,the medium dose group,high dose group and Benazepril group had the best effect.2.Effects of Qidigushen formula on renal tissue P53,PHB1,PHB2,PARP and cleaved PARP in IMN rats(1)Expression of P53,PHB1,PHB2 and cleaved PARP m RAN in renal tissue:Compared with blank group,PHB1 m RNA and PHB2 m RNA in model group were significantly decreased(P<0.01),P53 m RNA and cleaved PARP m RAN were significantly increased(P<0.01).Compared with model group,P53 m RNA in medium and high dose groups and benazepril group was significantly decreased(P<0.01),P53 m RNA in low dose group was decreased(P<0.05),PHB1 and PHB2 m RNA in medium and high dose groups and Benazepril group were significantly increased(P<0.01).The cleaved PARP m RAN of the other groups was significantly decreased(P<0.01).(2)Protein expression of P53,PHB1,PHB2,PARP and cleaved PARP in renal tissue:Compared with blank group,the proteins of P53 and cleaved PARP were significantly increased(P<0.01),and the proteins of PHB1,PHB2 and PARP were significantly decreased in the model group(P<0.01).Compared with the model group,P53 and cleaved PARP were significantly decreased in medium and high dose groups and benazepril groups(P<0.01),PHB1 protein was significantly increased in low,medium and high dose groups and Benazepril groups(P<0.01),and PHB2 protein was significantly increased in medium and high dose groups and Benazepril groups(P<0.01).PARP in Benazepril group and high dose group was significantly increased(P<0.01).Conclusion:Qidi Gushen Decoction can reduce urinary protein excretion,increase ALB and TP levels,and decrease TC and TG levels in IMN model rats;2.Qidi Gushen decoction can alleviate kidney pathological injury in IMN model rats;3.Qidigushen can inhibit the expression of P53 in IMN model rats,improve PHB1 and PHB2,reduce podocytes damage caused by mitochondrial dysfunction,and reduce proteinuria,thus achieving the efficacy of treating IMN. |
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