文献类型：期刊文献

中文题名：消脂化纤汤联合骨髓间充质干细胞移植对实验性非酒精性脂肪性肝炎肝硬化小鼠的干预作用及机制

英文题名：Effect of Xiaozhi Huaxian Decoction combined with bone marrow mesenchymal stem cells transplantation on experimental cirrhosis mice with non-alcoholic steatohepatitis and the underlying mechanism

作者：杨芳丽[1,2];王钰涵[3];姚凝[4];王昕[1];夏艳青[1,5];韩金孝[1,6];左小宁[1];秦英[1];王馨[4]

第一作者：杨芳丽

机构：[1]甘肃中医药大学中西医结合学院,甘肃兰州730000;[2]青海省交通医院老年医学科,青海西宁810008;[3]苏州大学苏州医学院,江苏苏州215123;[4]甘肃中医药大学第一临床医学院,甘肃兰州730000;[5]甘肃省兰州市第一人民医院风湿免疫科,甘肃兰州730050;[6]金川集团有限公司职工医院老年医学科,甘肃金昌737199

第一机构：甘肃中医药大学中西医结合学院

年份：2024

卷号：46

期号：11

起止页码：1843

中文期刊名：河北中医

外文期刊名：Hebei Journal of Traditional Chinese Medicine

收录：CSTPCD

基金：国家自然科学基金项目(编号:82160845);甘肃省自然科学基金项目(编号:20JR5RA181);甘肃省兰州市城关区科技计划项目(编号:2021-2-5);甘肃中医药大学引进人才科研启动基金项目(编号:2024YJRC-01);甘肃省教育厅高等学校创新基金(编号:2021B-173)。

语种：中文

中文关键词：肝硬化;非酒精性脂肪性肝炎;动物模型;小鼠;骨髓间充质干细胞;Th17细胞;动物实验;中药药理实验

外文关键词：Cirrhosis;Non-alcoholic steatohepatitis;Animal model;Mice;Bone marrow mesenchymal stem cells;Th17 cells;Animal experiment;Pharmacological experiment of traditional Chinese medicine

摘要：目的观察消脂化纤汤联合骨髓间充质干细胞(BM-MSCs)移植对实验性非酒精性脂肪性肝炎(NASH)肝硬化小鼠的干预作用及其可能机制。方法将40只健康SPF级C57BL/6小鼠随机分出8只作为空白组,其余32只小鼠采用蛋氨酸-胆碱缺乏(MCD)饮食联合10%四氯化碳(CCl4)腹腔注射诱导NASH肝硬化模型。造模成功后随机分为模型组、中药组、干细胞组、联合组,每组8只。其中中药组予消脂化纤汤灌胃,干细胞组行尾静脉注射BM-MSCs移植1次,联合组予消脂化纤汤灌胃的同时,行尾静脉注射BM-MSCs移植1次,空白组和模型组则不予任何干预。干预4周后取材,检测肝功能指标[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、白蛋白(ALB)],酶联免疫吸附法测定肝组织维A酸相关孤儿受体γt(RORγt)、白细胞介素23(IL-23)、IL-21、IL-17含量,酶联免疫吸附法测定血清及肝组织肝细胞生长因子(HGF)含量,逆转录聚合酶链式反应(RT-PCR)测定肝脏淋巴细胞RORγt、IL-23、IL-21、IL-17 mRNA表达水平。结果(1)与空白组比较,模型组血清ALT、AST含量均升高,ALB含量降低(P<0.01),与模型组比较,不同干预组各指标均有不同程度改善,以联合组变化最显著(P<0.01)。(2)肝组织IL-23、IL-21、RORγt、IL-17水平比较:与模型组比较,各干预组小鼠肝组织各指标均降低,联合组优于各单纯干预组(P<0.01)。(3)RT-PCR结果显示:与模型组比较,各干预组小鼠肝脏淋巴细胞RORγt、IL-23、IL-21、IL-17 mRNA表达降低,联合组优于各单纯干预组(P<0.05)。(4)各组小鼠血清和肝组织HGF表达水平比较:联合组优于中药组与干细胞组(P<0.01)。结论消脂化纤汤联合BM-MSCs移植可抑制肝脏过度炎症反应,从而促进肝脏细胞再生,其作用机制可能与调节辅助性T细胞17(Th17)免疫学功能相关。
Objective To investigate the intervention effect of Xiaozhi Huaxian Decoction combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on experimental cirrhosis mice with non-alcoholic steatohepatitis(NASH)and its possible mechanism.Methods A total of 40 healthy C57BL/6 mice in the specific pathogen-free(SPF)level were randomly divided into the blank group(n=8),and NASH plus cirrhosis group(n=32)induced by methionine-choline deficiency(MCD)diet combined with 10%carbon tetrachloride(CCl 4)intraperitoneal injection.After successful modeling,32 modeling mice were randomly divided into the model group,traditional Chinese medicine(TCM)group,BM-MSCs transplantation group,and TCM combined with BM-MSCs transplantation group.Mice in the TCM group were given Xiaozhi Huaxian Decoction by gavage,and those in the BM-MSCs transplantation group were given tail vein injection of BM-MSCs transplantation once.Mice in the TCM combined with BM-MSCs transplantation group were given both Xiaozhi Huaxian Decoction by gavage,and the tail vein injection of BM-MSCs transplantation once.Mice in the blank group and the model group were treated with blank control.Four weeks after interventions,liver function was detected by automatic biochemical analyzer,including the measurements of alanine transaminase(ALT),aspartate aminotransferase(AST)and albumin(ALB).The contents of retinoic acid-related orphan nuclear receptorγt(RORγt),interleukin-23(IL-23),IL-21,and IL-17 in liver tissue,and hepatocyte growth factor(HGF)in serum and liver tissue were determined by enzyme-linked immunosorbent assay(ELISA).The reverse transcription polymerase chain reaction(RT-PCR)was used to determine the mRNA levels of RORγt,IL-23,IL-21 and IL-17 in liver lymphocytes.Results Compared with the blank group,serum ALT and AST of the model group were significantly higher,and the serum ALB was significantly lower(P<0.01).Compared with the model group,the indexes of different treatment groups were improved at varied degrees,which was most pronounced in the TCM combined with BM-MSCs transplantation group(P<0.01).Compared with the model group,the indexes of liver function(IL-23,IL-21,RORγt,IL-17)in each treatment group were reduced at varied degrees,which were significantly better in the TCM combined with BM-MSCs group than the treatment group alone(P<0.01).RT-PCR results showed that compared with the model group,the mRNA expressions of RORγt,IL-23,IL-21 and IL-17 in liver lymphocytes of mice in each treatment group were significantly lower,which were significantly lower in the TCM combined with BM-MSCs group than the treatment group alone(P<0.05).Mice in the TCM combined with BM-MSCs group had significantly increased HGF level in serum and liver tissue than the remaining treatment groups(P<0.01).Conclusion Xiaozhi Huaxian Decoction combined with BM-MSCs transplantation can inhibit excessive inflammation in liver,thereby promoting liver cell regeneration in cirrhosis mice with NASH by regulating the immunological function of Th17 cells.