【摘要】 目的探讨甘草酸铵对过敏性紫癜性肾炎(HSPN)小鼠肾功能的影响及可能的作用机制。方法 2020年7月—2021年1月在邯郸市中心医院实验室进行实验,C57BL/6雄性小鼠80只,随机选取12只作为空白对照组,其余小鼠建立HSPN模型。将造模成功的60只小鼠随机分为模型组、环磷酰胺组(22 mg/kg)及甘草酸铵低、中、高剂量组(25、50、100 mg/kg),每组12只。环磷酰胺组、甘草酸铵各剂量组小鼠腹腔注射相应剂量的药物,1次/d,空白对照组和模型组给予等量生理盐水,持续4周。给药结束后,检测小鼠24 h尿蛋白水平和尿红细胞计数,血清白介素-23(IL-23)、IL-17、免疫球蛋白A(IgA)、尿素氮(BUN)、血肌酐(SCr)、循环免疫复合物(CIC)水平,外周血单个核细胞中Th17、Treg细胞占比及肾脏组织中IL-23、信号传导和转录激活因子3(STAT3)及其磷酸化蛋白表达水平;苏木素—伊红(HE)染色观察肾脏组织的形态学变化。结果与空白对照组比较,模型组小鼠24 h尿蛋白水平、尿红细胞计数,血清IL-23、IL-17、IgA、CIC、BUN、SCr水平,外周血单个核细胞中Th17细胞占比、Th17/Treg细胞比值,肾脏组织中IL-23、磷酸化STAT3(p-STAT3)/STAT3蛋白表达升高(P<0.05),Treg细胞占比显著降低(P<0.05),肾脏组织出现严重的病理损伤。与模型组比较,环磷酰胺组及甘草酸铵中、高剂量组小鼠24 h尿蛋白水平、尿红细胞计数,血清IL-23、IL-17、IgA、CIC、BUN、SCr水平,外周血单个核细胞中Th17细胞占比、Th17/Treg细胞比值,肾脏组织中IL-23、p-STAT3/STAT3蛋白表达降低(F/P=45.928/0.000、52.976/0.000、64.629/0.000、151.382/0.000、277.542/0.000、55.985/0.000、203.736/0.000、261.569/0.000、214.406/0.000、226.046/0.000、228.611/0.000、148.613/0.000),Treg细胞占比显著升高(F/P=24.160/0.000),肾脏组织病理损伤明显减轻。与环磷酰胺组比较,甘草酸铵高剂量组小鼠上述指标差异无统计学意义(P>0.05)。结论甘草酸铵可减轻HSPN小鼠肾损伤,其作用机制可能与抑制IL-23/STAT3通路的活化,调节Th17/Treg细胞免疫平衡有关。更多还原

【Abstract】 Objective To investigate the effect of ammonium glycyrrhizinate on renal function in mice with Henoch-Schonlein purpura nephritis(HSPN) and its possible mechanism.Methods The experiment was conducted in the Central Laboratory of Handan Central Hospital from July 2020 to January 2021. There were 80 C57 BL/6 male mice, 12 of which were randomly selected as the blank control group, and the other mice established HSPN model. Sixty successful mice were randomly divided into model group, cyclophosphamide group(22 mg/kg) and ammonium glycyrrhizate low, medium and high dose groups(25, 50 and 100 mg/kg), with 12 mice in each group. Mice in cyclophosphamide group and ammonium glycyrrhizinate groups were intraperitoneally injected with corresponding doses of drugs, once a day. The blank control group and model group were given the same amount of normal saline for 4 weeks. After administration, the levels of 24 h urinary protein, urinary red blood cell count, serum interleukin 23(IL-23), IL-17, immunoglobulin A(IGA), urea nitrogen(BUN), serum creatinine(SCR), circulating immune complex(CIC), the proportion of Th17 and Treg cells in peripheral blood mononuclear cells, IL-23 and signal transduction and transcription activator 3(STAT3) in renal tissue were measured And its phosphorylated protein expression level; Hematoxylin eosin(he) staining was used to observe the morphological changes of renal tissue. Results Compared with the blank control group, the 24-hour urinary protein level, urinary red blood cell count, serum IL-23, IL-17, IgA, CIC, bun and SCR levels, the proportion of Th17 cells and Th17/Treg cells in peripheral blood mononuclear cells, the expression of IL-23, phosphorylated STAT3(P-STAT3)/STAT3 protein in kidney tissue increased(P<0.05), and the proportion of Treg cells decreased significantly(P<0.05) Compared with the model group, the 24-hour urinary protein level, urinary red blood cell count, serum IL-23, IL-17, IgA, CIC, bun and SCR levels, the proportion of Th17 cells and the ratio of Th17/Treg cells in peripheral blood mononuclear cells, and the expression of IL-23 and P STAT3/STAT3 protein in renal tissue decreased in cyclophosphamide group and ammonium glycyrrhizate medium and high dose groups(F/P= 45.928/0.000, 52.976/0.000, 64.629/0.000, 151.382/0.000, 277.542/0.000, 55.985/0.000, 203.736/0.000, 261.569/0.000, 214.406/0.000, 226.046/0.000, 228.611/0.000, 148.613/0.000), the proportion of Treg cells increased significantly(F/P= 24.160/0.000) Compared with cyclophosphamide group, there was no significant difference in the above indexes in Ammonium Glycyrrhizinate high-dose group(P>0.05).Conclusion Ammonium glycyrrhizinate can reduce renal injury in HSPN mice, and its mechanism may be related to inhibiting the activation of IL-23/STAT3 pathway and regulating the immune balance of Th17/Treg cells.更多还原