目的 探讨水蛭冻干粉对糖尿病肾病大鼠肾组织损伤的保护作用。方法 SD大鼠随机选取8只作为对照组，其余大鼠给予高脂饲料喂养联合ip链脲佐菌素（35 mg/kg）建立糖尿病肾病模型，成模大鼠随机分为模型组及水蛭冻干粉低、中、高剂量（0.3、0.6、1.2 g/kg）组。给药16周后，检测大鼠24 h尿微量白蛋白（24 h urinary microalbumin，24 h-mALB）、空腹血糖、尿素氮（urea nitrogen，BUN）、肌酐（creatinine，Scr）水平和肾质量/体质量；采用TBA法和羟胺法测定大鼠血清超氧化物歧化酶（superoxide dismutase，SOD）活性和丙二醛（malondialdehyde，MDA）水平；采用ELISA法检测大鼠血清肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-1β（interleukin-1β，IL-1β）和单核细胞趋化因子-1（monocyte chemokine-1，MCP-1）水平；Western blotting法检测大鼠肾组织Janus蛋白酪氨酸激酶2/信号转导和转录激活子1、3（janus kinase 2/signal transducer and activator of transcription1、3，JAK2/STAT1/STAT3）通路相关蛋白表达。结果 与对照组比较，模型组大鼠24 h-mALB、空腹血糖、肾功能（BUN、Scr）、肾质量/体质量指标均显著升高（P<0.01），血清MDA、TNF-α、IL-1β和MCP-1水平显著增加（P<0.01），SOD活性显著降低（P<0.01），肾组织JAK2/STAT1/STAT3通路被激活（P<0.05、0.01）。与模型组比较，水蛭冻干粉组大鼠24 h-mALB排泄降低（P<0.01），肾功能（BUN、Scr）、肾质量/体质量改善（P<0.05、0.01），氧化损伤减轻（P<0.05、0.01），血清炎症因子水平下降（P<0.05、0.01），肾组织JAK2/STAT1/STAT3通路被抑制（P<0.05、0.01）。结论 水蛭冻干粉可能通过抑制糖尿病肾病大鼠氧化应激及炎症因子的产生，抑制肾组织JAK2/STAT1/STAT3信号通路活化，从而降低mALB排泄，改善肾功能，进而发挥肾脏保护作用。

Objective To explore the intervention of hirudo lyophilized powder in the renal tissue injury of diabetic nephropathy rats. Methods Eight SD rats were selected as control group, and the remaining rats were used to establish diabetic nephropathy models by high-fat diet combined with ip streptozotocin (35 mg/kg). Diabetic nephropathy rats were randomly divided into model group, hirudo lyophilized powder low-, medium-, high-dose (0.3, 0.6, 1.2 g/kg) group. After administered with corresponding drug for 16 weeks, the 24 h-urine microalbumin, blood glucose, urea nitrogen (BUN), creatinine (Scr) and KW/BW were detected; The activity of superoxide dismutase (SOD) and level of malondialdehyde (MDA) in serum were measured by TBA and hydroxylamine method respectively; The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemokine-1 (MCP-1) in serum were analyzed by ELISA; The related protein expressions of JAK2/STAT1/STAT3 pathway were detected in renal tissues by western blotting. Results Compared with control group, 24-h urine microalbumin, fasting blood glucose, BUN, Scr, and KW/BW were significantly increased (P<0.01); The serum levels of MDA, TNF-α, IL-1β, and MCP-1 were significantly increased (P<0.01); The activiy of SOD was significantly inhibited (P<0.01); The JAK2/STAT1/STAT3 signaling pathway was activated in renal tissues of model group (P<0.05, 0.01). Compared with model group, the 24 h urinary microalbumin excretion was reduced (P<0.01), renal function (BUN, Scr) and KW/BW were significantly improved (P<0.05, 0.01), the degree of oxidative stress and serum inflammatory factor levels were decreased (P<0.05, 0.01), and the activation of JAK2/STAT1/STAT3 signaling pathway was inhibited in hirudo lyophilized powder group (P<0.05, 0.01). Conclusion Hirudo lyophilized powder could inhibit oxidative stress and inflammation injury, inhibit the activation of JAK2/STAT1/STAT3 signaling pathway, reduce urinary microalbumin excretion, and improve renal function, and thus exert renal protective effects.

R285.5

国家自然科学基金资助项目（81373804）；河北省科研能力提升重点项目（KTZ2019024）