| Objective: To investigate the influence Zhenqing Recipe on expressions of renal transforming growth factorβ1 (TGF-β1) and plasminogen activator inhibitor-1(PAI-1) of Diabetic Rats. Studying the renal protective effect of Zhenqing Recipe on diabetic rats and investigating its partly mechanism.Methods: The T2DM rats were induced by high- sucrose -high- fat feeding and low dose injection of STZ。The male Wistar rats were randomly divided into normal control group,model group,Zhenqing Recipe treatment group and Lumbricus treatment group. At two time points : After a month of high- sucrose -high- fat feeding and one week after the injection of STZ, detecting blood insulin (FINS) level of each group rats; At four points : After a month of high- sucrose -high- fat feeding , one week after the injection of STZ, after 4 weeks and 8 weeks of administration , detecting fasting blood glucose (FBG), blood lipids (TC, TG) level; After 8 weeks of administration, plasma thromboxane B2(TXB2), tissue-type plasminogen activator (t-PA ) and plasminogen activator inhibitor -1(PAI-1) levels and urine albumin (UAE), 24h urine volume, serum creatinine (Scr) and urinary creatinine (Ucr) of all groups rats were measured , and then calculating the endogenous creatinine clearance rate (Ccr). After weighing the weight, rats were sacrificed, weighing the weight of kidney and calculating kidney weight index (KI); Using HE staining and PAS staining, to observe the structural changes of renal tissue under light microscope, and calculating extracellular matrix / glomerular area (ECM / GA); the expression of TGF-β1 and PAI-1 were located and preliminary quantified by immunohistochemistry; and the mRNA and protein expression of TGF-β1 and PAI-1 in renal cortex were determined respectively by RT-PCR and Western blotting. Results:1. After 1 month high- sucrose -high- fat diet, compared with the normal group, model group rats FBG was no significant difference (P> 0.05), serum TG and serum TC significantly increased (P <0.05), FINS increased significantly (P <0.01), insulin sensitivity index (ISI) decreased significantly (P <0.01). Showing insulin resistance has been successfully induced by high- sucrose -high- fat diet. 1 week after STZ injection, the model group FBG was significantly higher (P <0.01); its data reaches the standard of diabetes model; FINS was declined, but the difference was not significant (P> 0.05), although still higher than the normal group.2. Comparing with normal group, at the fourth week and the eighth week of treatment, the FBG, TC, TG of model group rats, Zhenqing Recipe treatment group rats and Lumbricus treatment rats were significantly higher (p<0.05 or p<0.01); After 8 weeks treatment, blood TXB2, blood PAI-1, urine albumin of model group rats, Zhenqing Recipe treatment group rats and Lumbricus treatment group rats were significantly increased(p<0.01) and blood t-PA, Ccr was significantly decreased (p<0.05 or p<0.01); renal tissue of model group rats apparentted pathological changes, KI and ECM / GA of model group rats were higher than normal group rats(p<0.01); TGF-β1, PAI-1 mRNA and protein expression of model group rats increased significantly compared with the control group rats (p<0.01).3. Comparing with model group, at the fourth week and the eighth week of treatment, the FBG, TG of Zhenqing Recipe treatment group were significantly decreased (p<0.01); the TC of the fourth week was no significant difference(p>0.05), the TC of the eighth week was significantly decreased (p<0.05). After 8 weeks treatment, blood TXB2 ,blood PAI-1, Urine albumin (p< 0.05 or p<0.01) were significantly decreased, blood t-PA, Ccr was significantly higher (p<0.01); renal pathology was lighter than the model group; KI and ECM / GA were lower than model group (p<0.05 or p<0.01); renal cortex TGF-β1, PAI-1 mRNA and protein levels of Zhenqing Recipe treatment group were significantly lower than the model group (p<0.01).4. Comparing with model group, at the fourth week and the eighth week of treatment, the FBG, serum TC of Lumbricus treatment group was no significant change; blood t-PA, Ccr was significantly higher (p<0.05); TG, serum TXB2, plasma PAI-1, UAE, KI, and ECM / GA, renal cortical TGF-β1, PAI-1 mRNA and protein levels were significantly lower than model group (p<0.01 or p<0.05). Renal pathological changes were alleviated compared with model group.Conclusion:Zhenqing Recipe can lower blood glucose, blood lipids, elevate blood levels of t-PA, decrease plasma PAI-1, TXB2 levels and lower urine albumin, increase Ccr of diabetic rats, inhibit diabetic nephroepathy ; reduce TGF-β1, PAI-1 protein and mRNA expressions of kidney , suggesting that Zhenqing Recipe can inhibit the expression of TGF-β1, leading to down-regulation of renal PAI-1 expression, which affecting the blood coagulation system and fibrinolysis and protecting renal function of diabetic rats.
|
PDF Full Text Request