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大黄酸对免疫球蛋白A肾病的改善作用及机制研究
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| 篇名： | 大黄酸对免疫球蛋白A肾病的改善作用及机制研究 |
| TITLE： | Study on improvement effects and mechanism of rhein on immunoglobulin A nephropathy |
| 摘要： | 目的 基于信号转导与转录激活因子3（STAT3）信号通路，研究大黄酸改善免疫球蛋白A肾病（IgAN）模型大鼠的作用及机制。方法将大鼠随机分为正常对照组、IgAN模型组和大黄酸治疗组（100mg/kg），每组10只。IgAN模型组和大黄酸治疗组采用牛血清白蛋白+脂多糖+四氯化碳联合法复制IgAN模型。造模第7周开始，大黄酸治疗组大鼠灌胃相应药物，正常对照组和模型组大鼠灌胃等量生理盐水，连续4周。末次给药后，检测大鼠尿红细胞数、24h尿蛋白（24h-UTP）以及血清中免疫球蛋白A（IgA）、小肠黏液中分泌型IgA（sIgA）的水平；观察大鼠肾皮质和小肠黏膜Peyer结的病理形态学变化以及肾皮质中IgA沉积情况；检测大鼠小肠黏膜Peyer结中白细胞介素17（IL-17）、IL-6和转化生长因子β（TGF-β）的表达水平；检测Peyer结中STAT3和维甲酸受体相关孤儿受体γ（tRORγt）mRNA的表达水平；检测Peyer结中磷酸化STAT3（p-STAT3）和RORγt蛋白的表达水平。结果与正常对照组比较，IgAN模型组大鼠尿红细胞数、24h-UTP以及血清中IgA、小肠黏液中sIgA水平均显著升高（P＜0.01）；肾皮质中肾小体增大，肾小囊扩张，球内系膜增生、纤维化明显；小肠黏膜Peyer结体积和生发中心增大；肾皮质中IgA沉积明显；小肠黏膜Peyer结中IL-17、IL-6、TGF-β、STAT3mRNA、RORγtmRNA以及p-STAT3、RORγt蛋白的表达水平均显著升高（P＜0.01）。与IgAN模型组比较，大黄酸治疗组大鼠上述指标水平均显著降低（P＜0.01），肾皮质病理损伤有所改善，小肠黏膜Peyer结体积和生发中心减小，肾皮质中IgA沉积减弱。结论大黄酸对IgAN模型大鼠具有较好的改善作用，其作用机制可能与抑制STAT3信号通路活性、调控小肠黏膜Peyer结内的免疫功能有关。 |
| ABSTRACT： | OBJECTIVE To study the improvement effects and mechanism of rhein on immunoglobulin A nephropathy （IgAN） model rat based on signal transducer and activator of transcription 3 （STAT3） signaling pathway. METHODS Rats were randomly divided into normal control group， IgAN model group and rhein treatment group， with 10 rats in each group. IgAN model group and rhein treatment group were given combination of bovine serum albumin+lipopolysaccharide+carbon tetrachloride to induce IgAN model. Since the 7th week， rhein treatment group rats were intragastrically given relevant medicine， and normal control group and model group rats were given equal amount of normal saline intragastrically， for consecutive 4 weeks. After the last administration， the count of urine sediment erythrocyte， 24 h-urine total protein （UTP）， the levels of immunoglobulin A （IgA） in serum and secretory immunoglobulin A （sIgA） in intestinal mucosa were detected. The pathological changes of Peyer’s patch in renal cortex and intestinal mucosa and IgA deposition in renal cortex were observed. The expressions of interleukin-17 （IL-17）， IL- 6 and transforming growth factor β （TGF-β） in Peyer’s patch of intestinal mucosa in rats were detected. The expressions of STAT3 and related orphan receptor γt （RORγt） mRNA in Peyer’s patch were detected. The expressions of p-STAT3 and RORγt proteins in Peyer’s patch were detected. RESULTS Compared with normal control group， the count of urine sediment erythrocyte， 24 h-UTP， the levels of IgA in serum and sIgA in intestinal mucosa were increased significantly in IgAN model group （P＜0.01）； enlarged renal corpuscles， dilated renal sacs， obvious intratubular mesangial hyperplasia and fibrosis were observed in renal cortex； the volume and germinal center of Peyer’s patch in intestinal mucosa increased； IgA deposition of renal cortex zxyylxk20220103） was obvious； the expressions of IL-17， IL-6 and TGF-β in Peyer’s patch， mRNA expressions of STAT3 and RORγt， protein expressions of p-STAT3 and RORγt were increased significantly （P＜0.01）. Compared with IgAN model group，above indexes were decreased significantly in rhein treatment group （P＜0.01）， pathological damage of renal cortex was improved， the volume of Peyer’s patch and germinal center of intestinal mucosa were reduced， and IgA deposition in renal cortex was weakened. CONCLUSIONS Rhein can improve IgAN model rats， the mechanism of which may be associated with inhibiting STAT3 signaling pathway and regulating immune function of Peyer’s patch in intestinal mucosa. |
| 期刊： | 2023年第34卷第07期 |
| 作者： | 陈杉杉；彭胜男；洪婷 |
| AUTHORS： | CHEN Shanshan，PENG Shengnan，HONG Ting |
| 关键字： | 大黄酸；免疫球蛋白A肾病；肠黏膜；Peyer结；信号转导与转录激活因子3信号通路 |
| KEYWORDS： | rhein； immunoglobulin A nephropathy； intestinal mucosa； Peyer’s patch； signal transducer and activator of |
| 阅读数： | 171 次 |
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