理气活血方调控MCP-1/JAK2/STAT3信号通路对慢性下肢缺血大鼠血管病变的影响  

Effect of regulating MCP-1/JAK2/STAT3 signal pathway with Liqi Huoxue decoction on vascular lesions in chronic lower limb ischemia rats

作　　者：金沐阳 王培利[2] 马鲁波[2,3] 刘剑刚 李天天[2] 张雯 于春利 JIN Muyang;WANG Peili;MA Lubo;LIU Jiangang;LI Tiantian;ZHANG Wen;YU Chunli;无(Xiyuan Clinical Medical College,China Academy of Chinese Medical Sciences,Beijing 100091,China;Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Guang’anmen Hospital,China Academy of Traditional Chinese Medicine,Beijing 100053,China)

机构地区：[1]北京中医药大学西苑临床医学院,北京100091 [2]中国中医科学院西苑医院,北京100091 [3]中国中医科学院广安门医院,北京100053

出　　处：《现代中西医结合杂志》2023年第6期747-753,共7页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：国家自然科学基金青年科学基金项目(81302979,81403411)。

摘　　要：目的基于趋化活化蛋白因子-1(MCP-1)/Janus激酶2(JAK2)/信号转导和转录激活因子3(STAT3)信号通路探讨理气活血方对球囊损伤糖尿病股动脉慢性下肢缺血大鼠的干预作用。方法选取清洁级雄性SD大鼠50只,随机取10只作为假手术组,给予普通饲料喂养和血管内导丝穿刺操作,不损伤股动脉;余40只大鼠通过高脂高糖饲料喂食和链脲佐菌素(STZ)腹腔注射方法构建糖尿病模型,然后在糖尿病模型基础上,应用血管内球囊损伤股动脉及髂动脉缩缝方法建立慢性下肢缺血模型。将造模成功大鼠随机分为模型组、辛伐他汀组、理气活血方高剂量组、理气活血方低剂量组,每组10只。辛伐他汀组给予辛伐他汀片1.80 mg/kg灌胃,理气活血方高、低剂量组分别给予理气活血方8.10 g生药/kg和4.05 g生药/kg灌胃,假手术组和模型组给予等容积纯净水灌胃,均1次/d,连续4周。全自动生化分析仪检测血糖、胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平,HE染色观察血管病理形态,电镜下观察股动脉内皮的病理形态,Real-time PCR和Western blot法分别检测股动脉中MCP-1、JAK2、STAT3 mRNA和蛋白表达情况。结果模型组大鼠血糖及血清TC、TG、LDL-C、IL-6、TNF-α水平均明显高于模型组(P均<0.05),辛伐他汀组与理气活血方高、低剂量组大鼠血清TC、TG、IL-6、TNF-α水平均明显低于模型组(P均<0.05)。病理观察,模型组大鼠血管内膜增厚,内皮血管平滑肌细胞增生,管腔狭窄,血管内皮拉伤,可见内弹力板、中膜断裂损伤;辛伐他汀组与理气活血方高、低剂量组大鼠内皮血管平滑肌细胞增生减少,管腔狭窄明显减轻,内皮损伤和断裂的内膜部分修复,裸露的内皮有部分覆盖。模型组大鼠股动脉中MCP-1、JAK2、STAT3 mRNA和蛋白相对表达量均明显高于假手术组Objective It is to explore the intervention effect of Liqi Huoxue decoction on chronic lower limb ischemia induced by balloon pressing femoral artery in rats with diabetes based on the monocyte chemoattractant protein-1(MCP-1)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signal pathway.Methods Fifty clean-grade male SD rats were selected,in which 10 ones were randomly selected as sham operation group and fed with normal diet and given intravascular wire puncture without damaging the femoral artery,and the remain 40 rats were fed with high-fat and high-sugar diet and given streptozotocin(STZ)intraperitoneal injection of to establish diabetes models.Based on the diabetes modeling,the blood flow in the femoral artery was restricted by intravascular balloon to simulate the chronic lower extremity ischemia caused by endothelial cell injury.The successfully modeled rats were randomly divided into model group,simvastatin group,high-dose group of Liqi Huoxue decoction,and low-dose group of Liqi Huoxue decoction,with 10 rats in each group.The simvastatin group was given simvastatin tablets 1.80 mg/kg by gavage,the high and low dose groups of Liqi Huoxue decoction were given Liqi Huoxue decoction 8.10 g crude drug and 4.05 g crude drug by gavage,respectively.The sham operation group and model group were given equal volume of pure water by gavage,all once a day,continuously treated for 4 weeks.The levels of blood glucose,cholesterol(TC),high density lipoprotein(HDL-C),low density lipoprotein(LDL-C),triglyceride(TG),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were determined by automatic biochemical analyzer,the pathological morphology of blood vessels was observed by HE staining,and the pathological morphology of the femoral artery endothelium was observed by electron microscopy,the mRNA and protein expressions of MCP-1,JAK2,and STAT3 in the femoral artery were respectively detected by Real time PCR and Western blot.Results The levels of blood glucose and serum TC,TG,LDL-C,IL-6,TN

关 键 词：理气活血方 下肢慢性缺血 趋化活化蛋白因子-1 JANUS激酶2 信号转导和转录激活因子3 炎症因子 

分 类 号：R-332[医药卫生]