通心络对早期糖尿病肾病大鼠肾功能及肾组织NO/eNOS表达的影响

Effects of Tong Xinluo on renal function and NO / e NOS expression in kidney in DN rats

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 investigate the influence of Tong Xinluo on renal function and the ex-pression of No, eNOS in kidney, and explore its mechanism of action. Methods The rat model was estab-lished by high fat feed and injection of streptozotocin. The model rats were separated into 3 groups random-ly：the model group（n=10）, the valsartan group（n=10） and Tong Xinluo group（n=10）. Another 10 normal rats were chosen as the normal group. Chinese herb medicine group was given Tong Xinluo 0. 4 g/（ kg·d） and Western medicine group was given valsartan 10 mg/（ kg·d） for 8 weeks. Fasting blood glu-cose（FBG）, Urinary albumin excretion（UAER） , serum creatinine（Scr）, blood urea nitrogen（BUN）, Creatinine clearance rate（ Ccr） were examined and calculated in 4weeks and 8weeks. After 8 weeks, all the rats were sacrificed, weighing their renal and observing the expression of NO, eNOS in kidney. Differ-ences among groups were assessed by one-way anova. Results Compared with normal group, the FBG, UAER , Scr , BUN, Ccr, kidney weight and relative kidney weight in model group are significantly in-creased（P〈0. 05）. Comperd with model group, the expression of FBG in valsartan group and Tong Xinluo group did not change（P〉0. 05）, while the UAER, Scr , BUN, Ccr, kidney weight and relative kidney weight significantly decreased（P〈0. 05）. The expression of NO, eNOS of TongXinluo group and valsartan group is also decreased（P〈0. 05）. Conclusion Tong Xinluo can decrease the expression of UAER, Scr , BUN, Ccr in DN rats, and then protect renal function. Decreasing the expression of NO and eNOS and then reducing glomerular hyperfiltration would be one of its action mechanism.