温补脾肾法对脾肾阳虚型UC大鼠JAK2/STAT3-SOCS6信号通路相关蛋白及基因表达的影响  

Effects of warming and tonifying spleen and kidney method on expressions of JAK2/STAT3-SOCS6 autophagy signal pathway related proteins and genes in UC rats with spleen-kidney Yang Deficiency

作　　者：李晓玲 吴玉泓(指导) 李海龙[1] 梁永林[1] 殷银霞 郝民琦 舍雅莉[1] LI Xiaoling;WU Yuhong;LI Hailong;LIANG Yonglin;YIN Yinxia;HAO Minqi;SHE Yali(Gansu University of Chinese Medicine,Lanzhou 730000,China)

机构地区：[1]甘肃中医药大学,兰州730000 [2]深圳大学附属华南医院,深圳518111 [3]北京中医药大学深圳医院(龙岗),深圳518116

出　　处：《中国免疫学杂志》2023年第8期1641-1646,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金项目(81860810);甘肃省中医药管理局项目(GZK-2018-5);敦煌医学与转化教育部重点实验室2018年度开放基金项目(DHYX18-17);甘肃中医药大学科学研究与创新基金项目(2019KCZD-5)。

摘　　要：目的:观察以温补脾肾法为指导的理中汤合四神丸对脾肾阳虚型溃疡性结肠炎(UC)大鼠模型病变结肠组织中JAK2、STAT3、p-STAT3、SOCS6蛋白及基因表达的影响。方法:采用病证结合造模方法复制脾肾阳虚型UC模型,成模大鼠随机分为模型组、柳氮磺砒啶组(SASP组)、理中汤合四神丸高、中、低剂量组,16只/组,同时设16只大鼠作为空白组。空白组与模型组给予蒸馏水灌胃,各治疗组给予对应的药物及剂量灌胃治疗,连续21 d。HE染色观察大鼠结肠黏膜组织病理变化;免疫组化法检测大鼠结肠黏膜组织中JAK2、STAT3、p-STAT3、SOCS6蛋白表达情况;RT-qPCR检测大鼠JAK2、STAT3、SOCS6mRNA表达情况;ELISA检测大鼠组织和血清中TGF-β1、ICAM-1含量。结果:与空白组相比,模型组大鼠结肠黏膜组织JAK2、STAT3、p-STAT3蛋白表达显著升高(P<0.01),JAK2、STAT3、p-STAT3蛋白着色深,表达呈强阳性,SOCS6蛋白表达显著降低(P<0.01),SOCS6蛋白着色浅,表达呈弱阳性。JAK2、STAT3 mRNA表达显著升高,SOCS6 mRNA表达显著降低(P<0.01),组织和血清中TGF-β1含量显著降低(P<0.01),ICAM-1含量显著升高(P<0.01);与模型组相比,中药高、中剂量组及SASP组JAK2、STAT3、p-STAT3蛋白表达显著降低(P<0.01),JAK2、STAT3、p-STAT3蛋白着色浅,表达呈弱阳性,SOCS6蛋白表达显著升高(P<0.01),SOCS6蛋白着色深,表达呈强阳性。JAK2、STAT3 mRNA表达显著降低(P<0.01),SOCS6 mRNA表达显著升高(P<0.01),组织和血清中TGF-β1含量显著升高(P<0.01),ICAM-1含量显著降低(P<0.01)。结论:以温补脾肾法为指导的理中汤合四神丸可能通过抑制JAK2/STAT3-SOCS6信号通路的激活,调节免疫系统平衡,修复受损结肠黏膜,达到治疗UC的目的。Objective:To observe the effects of Lizhong Decoction combined with Sishen Pills guided by the method of warming and tonifying the spleen and kidney on expressions of JAK2,STAT3,p-STAT3 and SOCS6 proteins and genes in diseased colon of rats with ulcerative colitis(UC)of spleen and kidney yang deficiency type.Methods:Models of spleen kidney yang UC were established by combining disease and syndrome.Rats were randomly divided into model group,sulfasalazine group(SASP group),Decoction combined with Sishen Pills high,medium and low doses groups,with 16 rats in each group,at the same time,16 rats were set up as blank group.Blank group and model group were given distilled water by gavage,and each treatment group was given corresponding drugs and doses by gavage for 21 days.Histopathological changes of colonic mucosa were observed by HE staining;expressions of JAK2,STAT3,p-STAT3 and SOCS6 proteins in rat colonic mucosa were detected by immunohistochemistry;RT-qPCR was used to detect expressions of JAK2,STAT3 and SOCS6 mRNA in rats;TGF-β1,ICAM-1 contents in tissues and serum of rats were detected by ELISA.Results:Compared with blank group,expressions of JAK2,STAT3 and p-STAT3 protein in colonic mucosa of model group were increased significantly(P<0.01),JAK2,STAT3 and p-STAT3 protein were deeply stained and strongly positive,while expression of SOCS6 protein was decreased significantly(P<0.01),SOCS6 protein was lightly stained and its expression was weakly positive.Expressions of JAK2 and STAT3 mRNA were increased significantly,while expression of SOCS6 mRNA was decreased significantly(P<0.01),and TGF-β1 in tissue and serum was decreased significantly(P<0.01),while content of ICAM-1 was increased significantly(P<0.01);compared with model group,expressions of JAK2,STAT3 and p-STAT3 protein of drug treatment groups were decreased significantly(P<0.01),JAK2,STAT3 and p-STAT3 protein were lightly stained,and their expressions were weakly positive,while expression of SOCS6 protein was increased significantly(P<0.01),SOCS6 pr

关 键 词：溃疡性结肠炎 温补脾肾法 理中汤合四神丸 免疫调节 JAK2/STAT3-SOCS6信号通路 

分 类 号：R285.5[医药卫生—中药学]