| Diabetic nephropathy is one of the most serious complications of diabetes, ofwhich the basic lesion is glomerular extracellular matrix (ECM) accumulation. Underdiabetic state, the imbalance of kidney ECM synthesis and degradation leading to theaccumulation of ECM, which have close relationships with matrixmetalloproteinase(MMPs) systems, fibrinolytic system (PA/PAI-1), and tissuetransglutaminase (tTG).Herba artemisiae capillaris is a traditional Chinese herbalmedicine, however, the research about applying herba artemisiae capillaris or itsextract (HACE) to diabetic nephropathy has not been reported. In this study, weobserved the protective effect of HACE on the kidneys of diabetic rats; then we testedthe effect of HACE on blood glucose, blood lipid, renal function, oxidative stress andrenal ECM accumulation; furthermore, in order to explore the deep protectivemechanisms from ECM degradation, we observed the effect of HACE on matrixmetalloproteinase (MMPs) as well as its inhibitor matrix metalloproteinase inhibitors(TIMPs), plasminogen activator inhibitor (PAI-1), and tissue transglutaminase（tTG）.The objective of the study is to provide theoretical basis for the prevention of HACEon DN.In this study, DN rats model were establish using streptozotocin (STZ)(55mg/kg). Then, the DN rat were treated with HACE low dose (2g/kg, HACE low group)and high dose (5g/kg, HACE high group) for12weeks, DN rat treated withbenazepril as a positive control(bena group) and normal rats as a blank control(controlgroup). Blood as well as urine biochemical indicators and oxidative stress indicatorswere detected; rats renal pathology and ECM accumulation were evaluated by HE,PAS and Masson staining; FN, Col Ⅳ, MMP-2, TIMP-2, PAI-1and tTG proteinexpression as well as distribution were analyzed by immunohistochemistry;TIMP-2,PAI-1and tTG content of renal cortex were detected by Western Blot;MMP-2activity was detected by zymography.The results showed DN rats in the present study demonstrated a significant highblood-glucose, renal dysfunction, ECM accumulation, pathological，alteration, and oxidativestress. The symptoms were evidently reduced by HACE treatment.Compared with the DN group, blood glucose group was significantly decreased (P<0.05), T-CHO and TG decreased significantly (P <0.01, P <0.05), renal tissue SOD,GSH-PX activity increased (P <0.01, P <0.05), MDA content decreased (P <0.05),kidney weight/body weight ratio decreased (P <0.05), albumin excretion ratedecreased significantly (P <0.05) in HACE high group. Compared with the DN group,basement membrane thickness, mesangial ECM accumulation attenuated in bothHACE groups, especially HACE high-dose group of which some indicators close tothose of the bena group. Immunohistochemistry showed that FN and Col Ⅳexpression in glomeruli significantly reduced after HACE treatment, and theexpression of inhibiter of ECM degradation as PAI-1, TIMP-2and tTG significantlyreduced. Western Blot displayed that to TIMP-2,PAI-1and tTG protein contentdecreased after HACE treatment. Enzymogram showed that MMP-2activity weresignificantly enhanced after HACE treatment, especially high dose group of whicheffect is similar to benazepril group.Based on the results we get the following conclusions:1. HACE can reduce blood sugar, blood lipids and oxidative stress inSTZ-induced diabetic rats, and prevent DN development.2. HACE can enhance MMP-2and PA activity of diabetic rat’s kidney; inhibitTIMP-2, PAI-1and tTG expression, then to promote ECM degradation and inhibitkidney ECM accumulation in STZ-induced diabetic rats.Innovations:This is the first time to observe the renal protective effect of HACE onSTZ-induced diabetic rats. The effect of HACE on the decisive factor in thedegradation of ECM (MMPs/TIMP, PA/PAI system and tTG) was analyzed toinvestigate the mechanisms from the ECM degradation level. |
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