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PNU282987对小鼠心脏重塑的改善作用及对JAK2/STAT3信号通路的影响
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| 篇名： | PNU282987对小鼠心脏重塑的改善作用及对JAK2/STAT3信号通路的影响 |
| TITLE： | Effects of PNU 282987 on Improving Cardiac Remodeling and JAK 2/STAT3 Signaling Pathway |
| 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40mg/kg）和PNU282987低、中、高剂量组（腹腔注射0.5、1.0、3.0mg/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，30mg/kg）7天以复制心脏重塑模型；各给药组小鼠均于ISO注射30min后给予相应药液，每天1次，连续7天。末次给药12h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。 |
| ABSTRACT： | OBJECTIVE：To st udy the effects of α7 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 PNU 282987 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 factor α（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-α and IL-6，the protein expression of ICAM- 1 and VCAM- 1，the ratio of p-JAK 2/JAK2 and p-STAT 3/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 medium-dose and high-dose groups were increased significantly ， HMI （except for PNU 282987 medium-dose group ），the contents of LDH （except for PNU 282987 medium-dose group ），CK，TNF-α and IL-6，the protein expression of ICAM- 1 and VCAM- 1，the ratio of p-JAK 2/JAK2 and p-STAT 3/STAT3 were decreased significantly （P＜0.05 or P＜ 0.01）；blue collagen deposition in the myocardial interstitium was significantly reduced ，and the degree of myocardial fibrosis was significantly reduced. There was no significant difference in the comparison of the above indicators in PNU 282987 low-dose group （P＞0.05）. CONCLUSIONS ：PNU282987 can improve cardiac remodeling of mice ，the mechanism of which may be associated with inhibiting JAK 2/STAT3 signaling pathway. |
| 期刊： | 2021年第32卷第10期 |
| 作者： | 方欢乐，李晓明，倪敏黾，赵玉文，杨永华 |
| AUTHORS： | FANG Huanle ，LI Xiaoming ，NI Minmin ，ZHAO Yuwen ，YANG Yonghua |
| 关键字： | 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 |
| KEYWORDS： | PNU282987；Isoproterenol；Cardiac remodeling ；Anti-inflammatory effect ；JAK2/STAT3 signaling pathway ；Mice |
| 阅读数： | 297 次 |
| 本月下载数： | 4 次 |
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