晕清降压方介导JAK2/STAT3通路改善肥胖性高血压瘦素抵抗的实验研究  

Study on the mechanism of Yunqing Jiangya Decoction mediated JAK2/STAT3 pathway improving leptin resistance in obese hypertension

作　　者：张艺 王思雨 杨晴 左丽婉 刘春华[1] ZHANG Yi;WANG Siyu;YANG Qing;ZUO Liwan;LIU Chunhua(The Second Hospital of Hunan University of Chinese Medicine,Changsha 410005,China)

机构地区：[1]湖南中医药大学第二附属医院心血管内科,长沙410005

出　　处：《环球中医药》2024年第11期2161-2169,共9页Global Traditional Chinese Medicine

基　　金：湖南省自然科学基金科药联合(2022JJ80021);湖南中医药大学一流学科重点项目(2021ZXYJH09);湖南中医药大学校级科研项目(2022CX165)。

摘　　要：目的探讨晕清降压方对痰瘀互结型肥胖性高血压模型大鼠降压减重的影响及可能作用机制。方法60只SD雄性大鼠随机选取8只为正常对照组,其余大鼠采用小剂量链脲佐菌素+高盐高脂饲料喂养+慢性束缚应激构建痰瘀互结型肥胖性高血压模型,按随机数字表法将造模成功的40只大鼠分为模型组、替米沙坦组、晕清降压方低、中、高剂量组,每组8只。晕清降压方低、中、高剂量组分别予晕清降压方10、20、40 g/(kg•d)灌胃;替米沙坦组予替米沙坦片3.5 mg/(kg•d)灌胃;正常对照组与模型组予蒸馏水10 mL/(kg•d)灌胃,每日1次,连续给药4周。测定各组血压、体质量;酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测血清瘦素(leptin,Lep)、血清血管紧张素II(angiotensinII,AngII)水平。蛋白免疫印迹(Western Blot)法检测下丘脑组织磷酸化Janus激酶2(phosphorylated Janus kinase 2,p-JAK2)/Janus激酶2(Janus kinase 2,JAK2)、磷酸化细胞信号传导与转录活化因子3(phosphorylated signal transducers and activators of transcription factor 3,p-STAT3)/细胞信号传导与转录活化因子3(signal transducers and activators of transcription factor 3,STAT3)、细胞因子信号传导抑制蛋白3(suppressor of cytokine signaling 3,SOCS3)蛋白表达;实时PCR法检测下丘脑组织血管紧张素II受体(angiotensin type 1 receptor,AT1R)、瘦素受体(leptin receptor,LepR)mRNA表达水平。免疫组化检测大鼠下丘脑LepR、AT1R蛋白表达水平。结果(1)与正常对照组比较,模型组体质量、血压显著升高(P<0.05);血清Lep、AngII含量显著升高(P<0.05);Western Blot显示p-JAK2/JAK2、p-STAT3/STAT3蛋白表达显著下降(P<0.05),SOCS3蛋白表达显著升高(P<0.05);实时PCR与免疫组化均显示LepR的表达下降(P<0.05),AT1R表达升高(P<0.05)。(2)与模型组比较,替米沙坦组体质量、血压均降低(P<0.05),p-JAK2/JAK2、p-STAT3/STAT3、SOCS3无统计学差异(P>0.05),实时PCR与免�Objective This study aimed to investigate the effects of Yunqing Jiangya Decoction on blood pressure reduction and weight loss in hypertensive obese rats with the phlegm-blood stasis syndrome and explore potential underlying mechanisms.Methods Sixty male Sprague-Dawley(SD)rats were randomly divided into six groups,with eight rats in the control group and the remaining rats subjected to a combination of low-dose STZ,high-salt high-fat diet,and chronic restraint stress to establish a hypertensive obese rat model with phlegm-blood stasis syndrome.The 40 model rats were further randomized into the model group,telmisartan group,and low,medium,and high-dose Yunqing Jiangya Decoction groups,8 rats in each group.Rats in the low,medium,and high-dose Yunqing Jiangya Decoction groups received oral gavage of 10,20,and 40 g/(kg•d)of Yunqing Jiangya Decoction,respectively,while the telmisartan group received telmisartan at a dose of 3.5 mg/(kg•d).The control group and the model group received distilled water 10 ml/(kg•d)by oral gavage.Treatment was administered once daily for four weeks,and blood pressure and body weight were measured.The levels of leptin(Lep)and angiotensin II(AngII)in serum were assessed using ELISA.Western blot was used to evaluate the expression of phosphorylated Janus kinase 2/Janus kinase 2(p-JAK2/JAK2),phosphorylated signal transducer and activator of transcription 3/signal transducer and activator of transcription 3(p-STAT3/STAT3),and suppressor of cytokine signaling 3(SOCS3)in the hypothalamic tissues.Real-time PCR was employed to determine the mRNA expression levels of angiotensin II receptor(AT1R)and leptin receptor(LepR)in the hypothalamic tissues.Immunohistochemistry was utilized to assess the protein expression levels of LepR and AT1R in the hypothalamus.Results(1)Compared with the normal control group,the body weight and blood pressure of the model group were significantly increased(P<0.05).The levels of Lep and AngII in serum increased significantly(P<0.05).Western Blot showed that the ex

关 键 词：肥胖性高血压 晕清降压方 瘦素抵抗 Janus激酶2/细胞信号传导与转录活化因子3信号通路 痰瘀互结 细胞因子信号传导抑制蛋白3 

分 类 号：R285.5[医药卫生—中药学]