CP-25抑制Th17细胞分化改善MRL/lpr狼疮小鼠肾损伤  

CP-25 inhibits Th17 cell differentiation and improves kidney injury in MRL/lpr lupus mice

作　　者：黄李娜 王盛付 王祥 徐靓 袁晓阳 蒯佳婕 魏伟[1] 严尚学[1] HUANG Li-na;WANG Sheng-fu;WANG Xiang;XU Liang;YUAN Xiao-yang;KUAI Jia-jie;WEI Wei;YAN Shang-xue(Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Team of Anti-inflammatory and Immunological Medicine Science and Technology Innovation in Anhui Universities, Hefei 230032, China)

机构地区：[1]安徽医科大学临床药理研究所,抗炎免疫药物教育部重点实验室,安徽抗炎免疫药物协同创新中心,安徽合肥230032

出　　处：《中国药理学通报》2021年第7期965-972,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81330081)。

摘　　要：目的研究芍药苷-6’-O-苯磺酸酯(CP-25)对MRL/lpr狼疮小鼠的治疗作用及其对Th17细胞功能的调节。方法随机将MRL/lpr小鼠分为模型组、CP-25(20、40、80 mg·kg^(-1))组和泼尼松(prednisone,Pre)组(5 mg·kg^(-1)),设BALB/c小鼠为正常对照。给药组每日给予相应药物,正常组与模型组给予溶媒。HE染色观察小鼠肾脏病理,流式检测小鼠脾脏中T细胞亚群比例;Western blot和qPCR法分别检测小鼠脾脏p-STAT3、RORγt蛋白表达及IL-17A mRNA水平;ELISA法检测血清中IL-17A和抗dsDNA抗体水平。体外诱导Th17细胞分化,观察CP-25对Th17分化、p-STAT3和RORγt蛋白和IL-17A mRNA水平的影响。结果CP-25可明显改善MRL/lpr小鼠肾脏病理,降低抗dsDNA、IL-17A水平;降低小鼠脾脏中CD3^(+)细胞、CD4^(+)CD69^(+)细胞和CD4^(+)IL-17^(+)Th17细胞比例;降低脾脏p-STAT3、RORγt蛋白表达及IL-17A mRNA水平。体外结果显示,CP-25可抑制Th17细胞分化,降低p-STAT3、RORγt表达。结论CP-25可改善MRL/lpr小鼠肾脏病理,其机制与抑制STAT3的磷酸化,调节Th17细胞分化有关。Aim To explore the role of paeoniflorin-6′-O-benzenesulfonate(CP-25)in MRL/lpr mice and theregulating action on Th17 cell differentiation.Methods MRL/lpr mice were randomly assigned to five groups as follows:model group,CP-25(20,40,80 mg·kg^(-1))group and prednisone group(5 mg·kg^(-1)).BALB/c mice were set as normal group.All mice were administered intragastrically everyday.The pathological changes of kidney tissues were observed by HE staining.The proportion of T cell subsets was detected by flow cytometry in mouse splenic lymphocytes;RORγt and phosphorylation-STAT3(p-STAT3)expression was detected by Western blot;the level of IL-17A mRNA was detected by qPCR;the levels of anti-dsDNA and interleukin 17A(IL-17A)were detected by ELISA.The differentiation of Th17 cells was induced in vitro,and the effects of CP-25 on the differentiation of Th17 cells and the levels of p-STAT3,RORγt and IL-17A mRNA were observed.Results CP-25 could obviously improve the kidney pathology of MRL/lpr mice,decrease the serum levels of anti-dsDNA and IL-17A in MRL/lpr mice,reduce the rate of CD3^(+) cells,CD4^(+)CD69^(+) cells and Th17 in the mouse splenic lymphocytes,inhibit the protein expression of p-STAT3,RORγt and IL-17A mRNA in splenic tissues.The results of in vitro experiments displayed that the differentiation of T cells into Th17 cells was inhibited by CP-25,and the expression of p-STAT3 and RORγt also decreased.Conclusions CP-25 could inhibit Th17 cell differentiation and improve kidney injury in MRL/lpr mice,and its mechanism is related to inhibiting STAT3 phosphorylation and regulating cell differentiation.

关 键 词：系统性红斑狼疮 MRL/LPR CP-25 TH17细胞 STAT3 RORΓT 

分 类 号：R-332[医药卫生] R284.1