【摘要】 目的 基于线粒体质量控制系统，探讨肾必宁颗粒对免疫球蛋白A(IgA)肾病大鼠的肾脏保护作用机制。方法 采用“牛血清白蛋白+四氯化碳+脂多糖”法建立IgA肾病模型，将模型大鼠随机分为模型组、醋酸泼尼松组（6.25 mg/kg）、肾必宁等剂量组（4.1 g/kg）和肾必宁高剂量组（20.5 g/kg），另取正常大鼠作为正常对照组，每组12只。各组大鼠灌胃相应药物或蒸馏水，每天1次，连续4周。末次给药后，检测大鼠24 h尿蛋白总量（24 h-UTP）和尿液中红细胞计数，以及血清肌酐（Scr）、尿素氮（BUN）、白蛋白（ALB）、丙氨酸转氨酶（ALT）水平；观察肾组织病理变化和肾脏系膜区IgA沉积改变；检测肾组织中PTEN诱导假定激酶1(PINK1)、E3泛素连接酶（Parkin）、微管相关蛋白1轻链3(LC3)、动力相关蛋白1(Drp1)、线粒体融合蛋白2(Mfn2) mRNA及蛋白表达水平。结果 与模型组比较，醋酸泼尼松组、肾必宁等剂量组和肾必宁高剂量组大鼠24 h-UTP，尿红细胞计数，ALT、BUN、Scr水平，LC3-Ⅱ/LC3-ⅠmRNA比值和Drp1 mRNA及蛋白表达水平均显著降低（P<0.05）;ALB水平，LC3-Ⅱ/LC3-Ⅰ蛋白比值和PINK1、Parkin、Mfn2 mRNA及蛋白表达水平均显著升高（P<0.05）；大鼠肾组织病理形态均明显改善，IgA沉积均明显减少。结论 肾必宁颗粒可能通过激活PINK1/Parkin通路、增强线粒体自噬、纠正线粒体动力学紊乱来减轻IgA肾病大鼠肾损伤，从而保护肾功能。更多还原

【Abstract】 OBJECTIVE To explore the renal protective mechanism of Shenbining granules on IgA nephropathy(IgAN) rats based on mitochondrial quality control system. METHODS IgAN rat model was established by the method of “bovine serum albumin+carbon tetrachloride+lipopolysaccharide”. The model rats were randomly divided into model group, prednisone acetate group(6.25 mg/kg), Shenbining equal-dose group(4.1 g/kg) and Shenbining high-dose group(20.5 g/kg). The normal rats were taken as the normal control group, with 12 rats in each group. Rats were given corresponding drugs or distilled water intragastrically in each group, once a day, for 4 consecutive weeks. After the last medication, the 24 h total urinary protein(24 hUTP) and erythrocyte count in urine were determined, and the levels of serum creatinine(Scr), blood urea nitrogen(BUN), albumin(ALB) and alanine transaminase(ALT) were also detected. The histopathological changes in the kidneys and changes in IgA deposition in the mesangial area of the kidney were observed. mRNA and protein expression levels of PTENinduced putative kinase 1(PINK1), E3 ubiquitin ligase(Parkin), microtubule-associated protein 1 light chain-3(LC3), dynamin-related protein 1(Drp1) and mitofusin 2(Mfn2) were detected in the kidney tissues of rats. RESULTS Compared with model group, 24 h-UTP, urinary erythrocyte count, ALT, BUN and Scr levels, LC3-Ⅱ/LC3-Ⅰ mRNA ratio, mRNA and protein expressions of Drp1 were reduced significantly in prednisone acetate group, Shenbining equal-dose group and Shenbining high-dose group(P<0.05); ALB level, LC3-Ⅱ/LC3-Ⅰ protein ratio, mRNA and protein expressions of PINK1, Parkin and Mfn2 were increased significantly(P<0.05); the pathological morphology of kidney tissue in rats was significantly improved, and IgA deposition was significantly reduced. CONCLUSIONS Shenbining granule may reduce renal pathological injury in IgAN rats and protect renal function by activating the PINK1/Parkin pathway, enhancing mitochondrial autophagy, and correcting mitochondrial kinetic disorders.更多还原