目的 探讨丹酚酸B对糖尿病肾病db/db小鼠肾纤维化和炎症的影响。方法 60只雄性db/db小鼠喂食高热量饲料1周后，给予丹酚酸B或厄贝沙坦干预8周，另取12只雄性db/m小鼠作为对照组。监测各组小鼠空腹血糖和体质量，采用全自动生化分析仪检测小鼠尿微量白蛋白（urinary microalbumin，mAlb）、尿肌酐（urine creatinine，UCr）和血液尿素氮（blood urea nitrogen，BUN）、三酰甘油（triglycerides，TG）、总胆固醇（total cholesterol，TC）含量；采用ELISA法检测小鼠肾组织中白细胞介素-6（interleukin-6，IL-6）和肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）含量；采用苏木素-伊红（HE）、Masson及PAS染色考察小鼠肾组织病理学变化；采用TUNEL染色观察小鼠肾组织细胞凋亡情况；采用免疫组化法检测小鼠肾组织中转化生长因子-β1（transforming growth factor-β1，TGF-β1）和IV型胶原（collagen type Ⅳ，Col-IV）蛋白表达情况；采用Western blotting法检测小鼠肾组织TGF-β1/Smad和核因子-κB（nuclear factor-κB，NF-κB）信号通路相关蛋白表达情况。结果 与模型组比较，丹酚酸B组小鼠空腹血糖和体质量降低（P<0.05），尿液mAlb和血液BUN、TC、TG水平均明显降低（P<0.05、0.01），尿液UCr水平明显升高（P<0.05）；肾组织TNF-α和IL-6水平显著降低（P<0.01）；肾组织病理损伤程度明显改善，肾组织细胞凋亡减少，肾组织TGF-β1和Col-IV蛋白表达减少；肾组织p-Smad2/Smad2蛋白表达水平显著升高（P<0.05、0.01），p-NF-κB p65/NF-κB p65、p-Smad3/Smad3和TGF-β1蛋白表达水平均显著降低（P<0.05、0.01）。结论 丹酚酸B能够改善糖尿病肾病db/db小鼠的肾纤维化和炎症反应，其机制可能与调控TGF-β1/Smad和NF-κB信号通路有关。

Objective To investigate the effect of salvianolic acid B on renal fibrosis and inflammation in diabetic nephropathy db/db mice. Methods Sixty male db/db mice were given salvianolic acid B or irbesartan for eight weeks of intervention after being fed a high-calorie diet for one week, and another 12 male db/m mice were selected as control group. Fasting blood glucose and body weight of mice in each group were monitored, automatic biochemical analyzer was used to detect the contents of urine microalbumin (mAlb), urine creatinine (UCr) and blood urea nitrogen (BUN), triglycerides (TG), total cholesterol (TC) in rats; ELISA method was used to detect interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) contents in kidney tissue; Hematoxylin-eosin (HE), Masson and PAS staining were used to observe the pathological changes of kidney tissue in mice; TUNEL staining was used to observe the apoptosis of kidney tissue in mice; Protein expressions of transforming growth factor-β1 (TGF-β1) and collagen type IV (Col-IV) in kidney tissue of mice were detected by immunohistochemistry; Western blotting was used to detect TGF-β1/Smad and nuclear factor-κB (NF-κB) signaling pathways related protein expressions of kidney tissue in mice. Results Compared with model group, fasting blood glucose and body weight of mice in salvianolic acid B group were decreased (P < 0.05), mAlb and BUN, TC, TG levels were significantly decreased (P < 0.05, 0.01), and UCr level in urine was significantly increased (P < 0.05); TNF-α and IL-6 levels in renal tissue were significantly decreased (P < 0.01); Degree of pathological damage in renal tissue was significantly improved, cell apoptosis of renal tissue and protein expressions of TGF-β1 and Col-IV in renal tissue were reduced; p-Smad2/Smad2 protein expression in kidney tissue was significantly increased (P < 0.05, 0.01), p-NF-κB p65/NF-κB p65, p-Smad3/Smad3 and TGF-β1 protein expressions were significantly decreased (P< 0.05, 0.01). Conclusion Salvianolic acid B can improve renal fibrosis and inflammation in diabetic nephropathy db/db mice, and its mechanism may be related to the regulation of TGF-β1/Smad and NF-κB signaling pathways.

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