PNU282987对小鼠心脏重塑的改善作用及对JAK2/STAT3信号通路的影响  

Effects of PNU282987 on Improving Cardiac Remodeling and JAK2/STAT3 Signaling Pathway

作　　者：方欢乐[1] 李晓明[1] 倪敏黾 赵玉文 杨永华[2] FANG Huanle;LI Xiaoming;NI Minmin;ZHAO Yuwen;YANG Yonghua(Medical College,Xi’an Peihua University,Xi’an 710125,China;Dept.of Pediatrics,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安培华学院医学院,西安710125 [2]西安交通大学第一附属医院儿科,西安710061

出　　处：《中国药房》2021年第10期1246-1251,共6页China Pharmacy

基　　金：陕西省重点研发计划项目(No.2021SF-362);西安培华学院校级重点课题(No.PHKT19010);西安培华学院大学生创新创业项目(No.PHDC2020045)。

摘　　要：目的:研究α7烟碱型乙酰胆碱受体激动剂PNU282987对小鼠心脏重塑的改善作用及对Janus激酶2/信号转导及转录激活因子3(JAK2/STAT3)信号通路的影响。方法:将雄性昆明种小鼠随机分为正常对照组、模型组、普萘洛尔组(阳性对照,灌胃40 mg/kg)和PNU282987低、中、高剂量组(腹腔注射0.5、1.0、3.0 mg/kg),每组10只。除正常对照组外,其余各组小鼠皮下注射异丙肾上腺素(ISO,30 mg/kg)7天以复制心脏重塑模型;各给药组小鼠均于ISO注射30 min后给予相应药液,每天1次,连续7天。末次给药12 h后,检测各组小鼠左室射血分数(EF)和左室短轴缩短率(FS),计算全心质量指数(HMI),观察其心肌组织形态学特征,测定血清中乳酸脱氢酶(LDH)、肌酸激酶(CK)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)含量和细胞间黏附分子1(ICAM-1)、血管细胞黏附分子1(VCAM-1)蛋白表达水平,检测心肌组织中磷酸化JAK2(p-JAK2)/JAK2、磷酸化STAT3(p-STAT3)/STAT3比值。结果:与正常对照组比较,模型组小鼠EF、FS均显著降低,HMI,LDH、CK、TNF-α、IL-6含量,ICAM-1、VCAM-1蛋白表达水平和p-JAK2/JAK2、p-STAT3/STAT3比值均显著升高(P<0.05或P<0.01),心肌间质蓝色胶原沉积明显,纤维化程度较重。与模型组比较,PNU282987中、高剂量组和普萘洛尔组小鼠EF、FS均显著升高,HMI(PNU282987中剂量组除外),LDH(PNU282987中剂量组除外)、CK、TNF-α、IL-6含量,ICAM-1、VCAM-1蛋白表达水平和p-JAK2/JAK2、p-STAT3/STAT3比值均显著降低(P<0.05或P<0.01),心肌间质蓝色胶原沉积明显减少,心肌纤维化程度明显降低;而PNU282987低剂量组小鼠上述指标变比较差异无明显变化(P>0.05)。结论:PNU282987可改善小鼠的心脏重塑,其机制可能与抑制JAK2/STAT3信号通路有关。OBJECTIVE:To study the effects ofα7 nicotinic acetylcholine receptor agonists(PNU282987)on improving cardiac remodeling of mice and Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway.METHODS:Male Kunming mice were randomly divided into normal control group,model group,propranolol group(positive control,i.g.40 mg/kg)and PNU282987 low-dose,medium-close and high-dose groups(intraperitoneal injection of 0.5,1.0,3.0 mg/kg),with 10 mice in each group.Except for the normal control group,mice in the other groups were given isoproterenol(ISO,30 mg/kg)subcutaneously for 7 days to induce the cardiac remodeling model.After 30 minutes of ISO injection,administration groups were given relevant liquid,once a day,for 7 consecutive days.Twelve hours after last administration,the left ventricular ejection fraction(EF)and left ventricular short axis shortening rate(FS)of mice in each group were measured,and the whole heart mass index(HMI)was calculated;the pathological changes of myocardium were observed.The serum contents of lactate dehydrogenase(LDH),creatine kinase(CK),tumor necrosis factorα(TNF-α),interleukin 6(IL-6),the protein expression of intercellular adhesion molecule 1(ICAM-1)and adhesion molecule 1(VCAM-1)were also determined.The ratios of p-JAK2/JAK2,p-STAT3/STAT3 in myocardial tissue were detected.RESULTS:Compared with normal control group,EF and FS of model group were significantly reduced,HMI,the contents of LDH,CK,TNF-αand IL-6,the protein expression of ICAM-1 and VCAM-1,the ratio of p-JAK2/JAK2 and p-STAT3/STAT3 were increased significantly(P<0.05 or P<0.01);blue collagen deposition in the interstitium of myocardium was obvious,and the degree of fibrosis was severe.Compared with model group,the EF and FS of the mice in the PNU282987 medium-dose and high-dose groups were increased significantly,HMI(except for PNU282987medium-dose group),the contents of LDH(except for PNU282987 medium-dose group),CK,TNF-αand IL-6,the protein expression of ICAM-1 and VCAM-1,the ratio o

关 键 词：PNU282987 异丙肾上腺素 心脏重塑 抗炎作用 Janus激酶2/信号转导及转录激活因子3信号通路 小鼠 

分 类 号：R542.2[医药卫生—心血管疾病] R965[医药卫生—内科学]