目的 观察益肾化湿颗粒对IgA肾病模型大鼠的治疗作用，并基于过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor γ，PPARγ）/核因子-κB（nuclear factor-κB，NF-κB）信号通路探讨其作用机制。方法 随机选取10只SD大鼠作为对照组，其余大鼠以“牛血清白蛋白＋四氯化碳＋脂多糖”联合用药免疫诱导的方法建立IgA肾病模型，IgA肾病大鼠随机分为模型组及益肾化湿颗粒低、高剂量（1.35、5.40 g/kg）组和泼尼松（5.40 mg/kg）组，每组15只。实验第7～14周，各给药组ig药物，对照组和模型组ig蒸馏水，1次/d，观察大鼠的一般状态。给药结束后，检测各组大鼠24 h尿蛋白，考察各组大鼠肾组织病理情况；采用免疫组化法检测各组大鼠肾组织肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和白细胞介素-6（interleukin-6，IL-6）蛋白阳性表达情况；采用Western blotting法检测各组大鼠肾组织PPARγ和NF-κB信号通路关键蛋白p65、p-p65蛋白表达情况。结果 益肾化湿颗粒能够显著降低IgA肾病大鼠24 h尿蛋白、尿素氮和血肌酐水平（P＜0.05、0.01），减少IgA肾病大鼠肾小球系膜区IgA沉积，显著降低肾组织TNF-α沉积（P＜0.05）；益肾化湿颗粒高剂量组大鼠肾组织p65和p-p65蛋白表达水平显著降低（P＜0.05），PPARγ蛋白表达水平显著升高（P＜0.05）。结论 益肾化湿颗粒能够减少IgA肾病大鼠24 h尿蛋白，改善肾功能及肾组织病理损伤，延缓IgA肾病进展，其作用机制可能与调控PPARγ/NF-κB通路有关。

Objective To investigate the therapeutic effect of Yishen Huashi Granules (益肾化湿颗粒) on IgA nephropathy rats, and explore its mechanism based on peroxisome proliferator-activated receptor γ (PPARγ)/nuclear factor-κB (NF-κB) signaling pathway. Methods Ten SD rats were randomly selected as control group. IgA nephropathy models were established in other rats by immune induction with the combination of bovine serum albumin, carbon tetrachloride and lipopolysaccharide. IgA nephropathy rats were randomly divided into model group, Yishen Huashi Granules low-, high-dose (1.35, 5.40 g/kg) groups and prednisone (5.40 mg/kg) group, with 15 rats in each group. During 7—14 weeks, rats in each administration group were ig drugs, rats in control group and model group were ig distilled water, once a day, the general state of rats were observed. After administration, 24 h urine protein of rats in each group was detected, and pathological condition of kidney tissue of rats in each group were investigated; Protein positive expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by immunohistochemical method; Western blotting was used to detect the protein expressions of PPARγ and NF-κB signaling pathway key proteins p65 and p-p65 in kidney tissues of rats in each group. Results Yishen Huashi Granules significantly reduced 24 h urine protein, urea nitrogen and blood creatinine levels of IgA nephropathy rats (P < 0.05, 0.01), reduced IgA deposition in glomerular mesangial area of ​​IgA nephropathy rats, and significantly reduced TNF-α deposition in renal tissue (P < 0.05); Protein expression levels of p65 and p-p65 in kidney tissue of rats in Yishen Huashi Granules high-dose group were significantly reduced (P < 0.05), and PPARγ protein expression level was significantly increased (P < 0.05). Conclusion Yishen Huashi Granules can reduce 24 h urine protein in rats with IgA nephropathy, improve renal function and renal tissue pathological damage, and delay the progression of IgA nephropathy. Its mechanism may be related to the regulation of PPARγ/NF-κB pathway.

R285.5

益肾化湿颗粒临床应用研究和基础研究开放课题（康药合字2020第336号）