目的：探究肾康注射液（SKI）对大鼠糖尿病肾病的保护作用及可能机制。方法：选取60只SD大鼠，随机分为正常组、糖尿病组、低、高剂量组四组各15只，糖尿病组、低、高剂量组大鼠进行糖尿病肾病模型建立，建模成功后分别使用2g/kg、4g/kg的肾康注射液对低、高剂量组大鼠进行干预，正常组、糖尿病组使用生理盐水干预。对四组大鼠血清甘油三酯（TG）、总胆固醇（TC）、空腹血糖（FBG）、糖化血红蛋白（HbA1c）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）、β2-MG、血清胱抑素C（CysC）、血肌酐（Scr）、血尿素氮（BUN）水平进行检测，检测四组大鼠肾重指数，并对肾组织中血管细胞粘附分子-1(VCAM-1)、细胞间黏附分子-1(ICAM-1)、白细胞介素-6（IL-6）、转化生长因子-β1（TGF-β1）、结缔组织生长因子（CTGF）、纤粘蛋白（FN）、COL-IV、α-SMA、血清超氧化物歧化酶（SOD）、丙二醛（MDA）、ROS水平及RhoA、ROCK1表达进行检测。结果：高剂量组大鼠FBG、FINS、TC、TG、HbA1c、HOMA-IR、β2-MG、CYS-C、SCr、BUN水平低于糖尿病组、低剂量组（P＜0.05）。高剂量组大鼠肾重及肾重指数低于低剂量组（P＜0.05）。高剂量组大鼠肾组织ICAM-1、VCAM-1、IL-6、TGF-β1、CTGF、FN、COL-IV、α-SMA、MDA、ROS水平低于糖尿病组、低剂量组，SOD水平高于糖尿病组、低剂量组（P＜0.05）。高剂量组大鼠肾组织RhoA、ROCK1相对表达量低于糖尿病组、低剂量组（P＜0.05）。结论：肾康注射液能够改善糖尿病肾病大鼠胰岛素抵抗及肾脏病变、细胞内皮损伤、慢性炎症、氧化应激以及肾间质纤维化状况，RhoA/ROCK信号通路可能是肾康注射液对大鼠糖尿病肾病起到保护作用机制之一。

【Abstract】Objective:To explore the protective effect and possible mechanism of Shenkang injection (SKI) on diabetic nephropathy in rats. Methods:Sixty SD rats were randomly divided into four groups: normal group, diabetic group, low-dose group and high-dose group, with 15 rats in each group. Diabetic nephropathy model was established in diabetic group, low-dose group and high-dose group. After successful modeling, Shenkang injection of 2 g/kg and 4 g/kg was used to intervene the rats in low-dose and high-dose groups, and normal group and diabetic group were intervened with normal saline. Group B was treated with saline. Serum triglyceride (TG), total cholesterol (TC), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), insulin resistance index (HOMA-IR), β-2-MG, serum cystatin C (CysC), serum creatinine (Scr) and blood urea nitrogen (BUN) levels were measured in four groups of rats. Renal weight index (RWI) and vascular fineness in renal tissue were measured. Cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), transforming growth factor-β 1 (TGF-β 1), connective tissue growth factor (CTGF), fibronectin (FN), COL-IV, α-SMA, serum superoxide dismutase (SOD), malondialdehyde (MDA), ROS levels and the expression of RhoA and ROCK1 were detected. Results:The levels of FBG, FINS, TC, TG, HbA1c, HOMA-IR, β 2-MG, CYS-C, SCr, BUN in the high dose group were lower than those in the diabetic group and the low dose group (P < 0.05).The kidney weight and kidney weight index of rats in the high dose group were lower than those in the low dose group (P < 0.05).The levels of ICAM-1, VCAM-1, IL-6, TGF-β 1, CTGF, FN, COL-IV, α-SMA, MDA and ROS in the kidney tissue of rats in the high dose group were lower than those in the diabetic group and the low dose group, and the levels of SOD were higher than those in the diabetic group and the low dose group (P < 0.05).The relative expression of RhoA and ROCK1 in kidney tissue of rats in high dose group was lower than that in diabetic group and low dose group (P < 0.05). Conclusion:Shenkang injection can improve insulin resistance and renal pathological changes, endothelial damage, chronic inflammation, oxidative stress and renal interstitial fibrosis in diabetic nephropathy rats. RhoA/ROCK signaling pathway may be one of the protective mechanisms of Shenkang injection on diabetic nephropathy in rats.

武汉市卫计委课题(编号wz15d10)