摘要
目的观察甘草泻心汤对溃疡性结肠炎模型大鼠的疗效和IL-6/STAT3信号通路中相关分子的调节作用,以揭示其治疗溃疡性结肠炎的作用机制及安全性。方法将60只SD大鼠随机分为空白组,模型组,美沙拉嗪组,甘草泻心汤低、中、高剂量组6组。以TNBS/乙醇法造模后分别以生理盐水、美沙拉嗪及甘草泻心汤各剂量灌胃。14d后检测血清ALT、AST、BUN及Cr含量,HE染色观察结肠组织结构改变,免疫组化分析结肠组织IL-6、STAT3及磷酸化STAT3的蛋白表达,以qPCR法检测结肠组织IL-6及STAT3的mRNA表达。结果与空白组比较,模型组血清AST含量明显升高(P<0.01),而ALT、BUN、Cr无明显变化(P>0.05),结肠组织病理评分明显增加(P<0.01),结肠组织IL-6和STAT3的蛋白和mRNA表达均明显增高(P<0.01),且STAT3活化明显增加(P<0.01)。与模型组比较,甘草泻心汤各剂量组血清AST含量明显降低(P<0.01),美沙拉嗪组及甘草泻心汤中剂量组结肠组织病理评分明显降低(P<0.01),结肠组织IL-6、STAT3和磷酸化STAT3的蛋白表达明显降低(P<0.01),IL-6和STAT3的mRNA表达明显降低(P<0.01)。结论甘草泻心汤能改善溃疡性结肠炎模型大鼠结肠病理结构改变,尤以中剂量明显。其作用机制可能与降低结肠组织中IL-6水平,抑制IL-6/STAT3信号转导通路,降低STAT3表达与活化有关。甘草泻心汤对TNBS溃疡性结肠炎模型大鼠的治疗安全有效。
OBJECTIVE To observe the curative effect of Gancao Xiexin Decoction(GCXXT)on ulcerative colitis(UC)model rats and explore the regulation mechanism of related molecules in the pathways of IL-6/STAT3.METHODS 60 SD rats were randomly divided into 6 groups:control,TNBS/ethanol,mesalazine and GCXXT(2.93,5.86,11.72 g/kg)groups.Blood serum was extracted to detect the content of ALT,AST,BUN and Cr.Colon tissues were observed by optical microscope.The expressions of protein of IL-6,STAT3 and phosphate STAT3 were evaluated by immunohistochemistry.The expressions of mRNA of IL-6 and STAT3 were analyzed by qPCR.RESULTS Compared with the blank group,AST in serum of model group increased obviously(P<0.01).However,ALT,BUN and Cr displayed no change(P>0.05).Pathological scores of colon tissues of model group increased significantly(P<0.01).The expressions of protein and mRNA of IL-6 and STAT3 in colon tissues increased in model group(P<0.01).Furthermore,the activation of STAT3 increased(P<0.01).Compared with the model group,AST in serum of rats of three groups treated with GCXXT decreased(P<0.01).Pathological scores of colon tissues of mesalazine group and medium dose GCXXT group decreased significantly(P<0.01).After the treatment of mesalazine or GCXXT,the expression of protein of IL-6,STAT3 and phosphate STAT3 reduced(P<0.01).The expression of mRNA of IL-6 and STAT3 decreased(P<0.01).CONCLUSION GCXXT can alleviate the pathological changes of colon,and medium dose of it can lead to satisfactory results.The mechanism may be related to its abilities to decrease expression of IL-6 in colonic tissue,inhibit IL-6/STAT3 signaling pathway and reduce the expression and activation of STAT3.These results showed that GCXXT is effective and safe in ameliorating ulcerative colitis.
出处
《南京中医药大学学报》
CAS
CSCD
北大核心
2017年第6期627-632,共6页
Journal of Nanjing University of Traditional Chinese Medicine
基金
江苏省中医药局科技项目(YB2015181)
关键词
溃疡性结肠炎
甘草泻心汤
白介素-6
信号转导转录激活因子3
ulcerative colitis
Gancao Xiexin decoction
interleukin-6
signal transducer and activator of transcription 3
