Department of Nephrology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
Department of Pathology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
J Ethnopharmacol. 2023 May 10;307:116220. doi: 10.1016/j.jep.2023.116220. Epub 2023 Feb 5.
Immunoglobulin A nephropathy (IgAN) is an immune-related primary glomerular disease prevalent worldwide, with complicated clinical manifestations and an unclear pathogenesis. IgAN is the main cause of chronic renal failure and places a significant burden on patients and society. The modified Huangqi Chifeng decoction (MHCD) is an effective prescription for the clinical treatment of IgAN while its specific mechanism remains to be further elucidated.
Based on the findings of previous network pharmacology-related method-based studies, this study aimed to further explore the mechanism of action of MHCD for IgAN treatment.
IgAN rat model was established by bovine serum protein + carbon tetrachloride + lipopolysaccharide. After successful modeling, the rats in the original model group were divided into 5 group: model group, telmisartan group, and MHCD high-, medium- and low-dose groups by random number table (n = 10 respectively). The corresponding drugs were applied for 8 weeks, and the experiment lasted for 21 weeks. At the end of the experiment, 24h urine protein quantification, serum biochemistry and IL-6 and IL-17A levels were measured. The pathological changes of kidney were observed by light microscope, immunofluorescence microscope and the changes of glomerular ultrastructure were observed by transmission electron microscope. The expression levels of IL-17 signaling pathway related proteins (HSP90, MMP9, NF-κB P65 and p-NF-κB P65) were detected by Western Blot and immunohistochemistry.
Telmisartan and MHCD treatment can reduce the 24h urinary protein level and improved blood stasis states of IgAN rats, alleviate the renal pathological injury, decrease the serum levels of IL-6, IL-17A and the expression levels of HSP90, MMP9 and p-NF-κB P65 related proteins in IL-17 signaling pathway.
MHCD can down-regulate the expression of IL-17 signaling pathway-related factors in IgAN model rats, improve the state of blood stasis, and alleviate the pathological damage of kidney in rats.
免疫球蛋白 A 肾病(IgAN)是一种全球性流行的与免疫相关的原发性肾小球疾病,临床表现复杂,发病机制尚不清楚。IgAN 是慢性肾衰竭的主要病因,给患者和社会带来了沉重的负担。改良黄芪赤风汤(MHCD)是治疗 IgAN 的有效方剂,但具体机制仍需进一步阐明。
基于前期网络药理学相关方法学研究的结果,本研究旨在进一步探讨 MHCD 治疗 IgAN 的作用机制。
采用牛血清蛋白+四氯化碳+脂多糖法建立 IgAN 大鼠模型。模型成功建立后,将原模型组大鼠按随机数字表法分为 5 组:模型组、替米沙坦组和 MHCD 高、中、低剂量组(n 分别为 10 只)。分别给予相应药物治疗 8 周,实验共 21 周。实验结束时,检测 24h 尿蛋白定量、血清生化及 IL-6、IL-17A 水平,光镜、免疫荧光镜观察肾脏病理变化,透射电镜观察肾小球超微结构变化,Western blot 和免疫组化法检测 IL-17 信号通路相关蛋白(HSP90、MMP9、NF-κB P65 和 p-NF-κB P65)的表达水平。
替米沙坦和 MHCD 治疗可降低 IgAN 大鼠 24h 尿蛋白水平,改善血液瘀滞状态,减轻肾脏病理损伤,降低血清 IL-6、IL-17A 水平及 IL-17 信号通路中 HSP90、MMP9 和 p-NF-κB P65 相关蛋白的表达水平。
MHCD 可下调 IgAN 模型大鼠 IL-17 信号通路相关因子的表达,改善血液瘀滞状态,减轻大鼠肾脏的病理损伤。