绿原酸通过cGAS-STING信号通路改善慢性肾小球肾炎大鼠的T淋巴细胞免疫  

Chlorogenic acid improves T lymphocyte immunity in rats with chronic glomerulonephritis through cGAS-STING signal pathway

作　　者：余婷 谢宇端 刘晶 钱晨 李伟[5] YU Ting;XIE Yuduan;LIU Jing;QIAN Chen;LI Wei(Department of Laboratory,Wuhan Mental Health Center,Wuhan 430012,China;Department of Laboratory,Wang Jing Hospital of CACMS,Beijing 100102,China;Department of Nursing,Wuhan Mental Health Center,Wuhan 430012,China;Psychological Consultation and Treatment Center,Wuhan Mental Health Center,Wuhan 430012,China;Department 2 of Internal Medicine,Wang Jing Hospital of CACMS,Beijing 100102,China)

机构地区：[1]武汉市精神卫生中心检验科,430012 [2]中国中医科学院望京医院检验科,北京100102 [3]武汉市精神卫生中心护理部,430012 [4]武汉市精神卫生中心心理咨询与治疗中心,430012 [5]中国中医科学院望京医院内二科,北京100102

出　　处：《免疫学杂志》2023年第9期737-745,共9页Immunological Journal

基　　金：武汉市医学科研项目(WG21Q04)。

摘　　要：目的探究绿原酸通过环状GMP-AMP合成酶(c GAS)-干扰素基因刺激因子(STING)信号通路对慢性肾小球肾炎(CGN)大鼠的免疫调节作用。方法取SD大鼠注射阳离子化牛血清白蛋白(C-BSA)诱导建立CGN模型,随机分为模型组、绿原酸低剂量(60 mg/kg)组、绿原酸高剂量(120 mg/kg)组、绿原酸高剂量(120 mg/kg)+空载组、绿原酸高剂量(120 mg/kg)+cGAS过表达组,每组10只,另取10只SD大鼠注射等剂量生理盐水作为对照组,分组处理后测定肾功能指标-24 h尿蛋白含量和血清肌酐(Scr)、血尿素氮(BUN)水平;苏木素-伊红(HE)染色检测肾组织病理形态;免疫荧光染色检测肾组织IgG沉积;流式细胞术检测外周血CD4^(+)、CD8^(+)T淋巴细胞比例;酶联免疫吸附实验(ELISA)检测血清炎性相关因子-肿瘤坏死因子α(TNF-α)、γ干扰素(IFN-γ)、白细胞介素10(IL-10)水平;免疫印迹法检测肾组织cGAS-STING信号通路蛋白表达。结果与模型组相比,绿原酸低剂量组、绿原酸高剂量组大鼠肾组织病理损伤均减轻,外周血CD4^(+)T淋巴细胞比例、血清IL-10水平均升高,24 h尿蛋白含量、Scr及BUN水平、肾组织IgG沉积的免疫荧光相对强度、CD8^(+)T淋巴细胞比例、血清TNF-α及IFN-γ水平、肾组织c GAS及STING蛋白表达均降低(P<0.05),绿原酸高剂量组的效果更好。c GAS过表达可逆转高剂量绿原酸对上述各个指标的影响(P<0.05)。结论绿原酸可抑制炎症反应,减轻CGN大鼠肾组织IgG沉积,通过影响T淋巴细胞而调节免疫,最终改善其肾功能,其机制可能与抑制cGAS-STING信号通路有关。This study was designed to investigate the immunoregulatory effect of chlorogenic acid on chronic glomerulonephritis(CGN)rats through the cyclic GMP-AMP synthetase(cGAS)-stimulator of interferon genes(STING)signal pathway.SD rats were injected with cationic bovine serum albumin(C-BSA)to induce CGN model,then the model rats were randomly grouped into model group,low-dose chlorogenic acid(60 mg/kg)group,highdose chlorogenic acid(120 mg/kg)group,high-dose chlorogenic acid(120 mg/kg)+empty load group,and high-dose chlorogenic acid(120 mg/kg)+cGAS overexpression group,with 10 rats in each group.Another 10 SD rats were injected with the same-dose of normal saline as the control group.The renal function indexes were measured,including the content of 24 h urine protein and the levels of serum creatinine(Scr)and blood urea nitrogen(BUN);hematoxylin-eosin(HE)staining was applied to detect the renal pathological morphology;immunofluorescence staining was applied to detect the deposition of IgG in renal tissue;flow cytometry was used to detect the proportions of CD4^(+)and CD8^(+)T lymphocytes in peripheral blood;ELISA was applied to detect the levels of serum inflammatory related factors-tumor necrosis factor-α(TNF-α),γ-interferon(IFN-γ)and interleukin-10(IL-10);and immunoblotting was applied to detect the expression of cGASSTING signal pathway protein in kidney tissue.Compared with the model group,the pathological damage of kidney tissue of rats in the two chlorogenic acid groups were reduced,the proportion of CD4^(+)T lymphocytes in peripheral blood and the level of IL-10 in serum increased,the 24 h urine protein content,the levels of Scr and BUN,the relative intensity of immunofluorescence of IgG deposition in renal tissue,the ratio of CD8^(+)T lymphocytes,the levels of serum TNF-αand IFN-γ,and the expression of cGAS and STING proteins in renal tissue all decreased(P<0.05),and the effect of high dose of chlorogenic acid was better.Overexpression of cGAS can reverse the effects of chlorogenic acid on the above index

关 键 词：绿原酸 cGAS-STING 慢性肾小球肾炎 免疫调节 

分 类 号：R692.31[医药卫生—泌尿科学]