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目的观察通心络对高脂饲料联合小剂量链脲佐菌素(streptozotocin,STZ)诱导的早期糖尿病肾病(diabetic nephropathy,DN)大鼠血清一氧化氮(nitric oxid,NO)含量及内皮型一氧化氮合酶(e NOS)蛋白表达的影响,探讨通心络防治早期DN大鼠肾小球高滤过的作用机制。方法采用高脂饲料联合小剂量STZ建立DN大鼠模型,将DN大鼠随机分为模型组、缬沙坦组、通心络组各10只,设立10只正常SD大鼠为空白组,通心络组给予通心络超微粉0.4 g/(kg·d),缬沙坦组给予缬沙坦10 mg/(kg·d)干预8周,于治疗4周、8周监测空腹血糖(fasting blood glucose,FBG),尿微量白蛋白排泄率(urinary albumin excretion,UAER)、血肌酐(serum creatinine,SCr)及尿素氮(blood urea nitrogen,BUN),并计算内生肌酐清除率(creatinine clearance rate,Ccr)。于8周末处死大鼠,称量肾重,计算肾重指数,检测肾组织NO含量及e NOS蛋白表达。多组组间差异比较采用单因素方差分析。结果与空白组比较,模型组大鼠FBG、UAER、肾重及肾重指数、Scr、BUN、Ccr、NO含量显著升高、e NOS蛋白表达显著增强(P<0.05)。与模型组比较,通心络组及缬沙坦组FBG无明显变化(P>0.05),UAER、Scr、BUN、Ccr、肾重及肾重指数显著下降(P<0.05)。通心络组及缬沙坦组肾组织NO含量较模型组显著降低,e NOS蛋白表达较模型组减弱(P<0.05)。结论通心络可降低早期DN大鼠UAER、Scr、BUN、Ccr、肾重及肾重指数,保护肾功能。通心络抑制肾组织e NOS蛋白表达,减少肾组织NO的含量,从而降低早期DN大鼠肾小球率过滤,可能是通心络改善肾小球早期高滤过的作用机制之一。
Objective To observe the effect of Tongxinluo on the content of nitric oxide (NO) in early diabetic nephropathy (DN) induced by high fat diet combined with low dose streptozotocin (STZ) Nitric oxide synthase (e NOS) protein expression, explore the role of Tongxinluo prevention and treatment of early glomerular hyperfiltration in DN rats. Methods DN rats were induced by high-fat diet combined with low-dose STZ. DN rats were randomly divided into model group, Valsartan group and Tongxinluo group. Ten normal SD rats were randomly divided into blank group The Xinluo group received 0.4 g / (kg · d) of Tongxinluo micronized powder and the Valsartan group was given Valsartan 10 mg / (kg · d) for 8 weeks. After 4 and 8 weeks of treatment, fasting blood glucose blood glucose (FBG), urinary albumin excretion (UAER), serum creatinine (SCr) and blood urea nitrogen (BUN) were calculated. The creatinine clearance rate , Ccr). The rats were sacrificed at the end of the 8th week. The kidney weights were weighed and the kidney index was calculated. The content of NO in the kidney and the expression of eNOS protein were detected. Multi-group differences were compared using one-way analysis of variance. Results Compared with the blank group, the content of FBG, UAER, kidney weight, kidney index, Scr, BUN, Ccr and NO in model group were significantly increased and eNOS protein expression was significantly increased (P <0.05). Compared with the model group, the FBG of Tongxinluo group and valsartan group had no significant change (P> 0.05), and the levels of UAER, Scr, BUN, Ccr, kidney weight and kidney weight index decreased significantly (P <0.05). The NO content in Tongxinluo group and valsartan group was significantly lower than that in model group, and the expression of eNOS protein was weaker than that in model group (P <0.05). Conclusion Tongxinluo can reduce the early diabetic rats UAER, Scr, BUN, Ccr, kidney weight and kidney index, protect renal function. Tongxinluo inhibition of eNOS protein expression in renal tissue and reduce the content of NO in renal tissue, thereby reducing the rate of early DN rat glomerular filtration rate may be one of the mechanisms of Tongxinluo improve glomerular early hyperfiltration.