心力衰竭大鼠延髓腹外侧区磷脂酰肌醇3激酶信号表达对下丘脑室旁核神经炎症的影响  

Effect of phosphoinositide-3 kinase signaling in the rostral ventrolateral medulla on neuroinflammation in the hypothalamic paraventricular nucleus in heart failure rats

作　　者：王宇 张生长 沈媛媛 林加锋[2] WANG Yu;ZHANG Shengchang;SHEN Yuanyuan;LIN Jiafeng(Department of Cardiology,Yueqing Hospital Affiliated to Wenzhou Medical University,Wenzhou 325600,China)

机构地区：[1]浙江温州医科大学附属乐清医院心血管内科,325600 [2]温州医科大学附属第二医院心血管内科

出　　处：《心肺血管病杂志》2020年第10期1264-1270,1285,共8页Journal of Cardiovascular and Pulmonary Diseases

摘　　要：目的:探讨延髓腹外侧区(RVLM)中的PI3K基因沉默对心力衰竭(HF)大鼠下丘脑室旁核(PVN)的神经炎症影响。方法:雄性大鼠接受PI3K shRNA或Con shRNA的RVLM显微注射。1周后,对部分大鼠实施安乐死以确认shRNA的转染潜力和敲除效率。其余大鼠则进行冠状动脉结扎以诱导HF或假手术。结果:冠状动脉结扎术后4周,与HF+Con shRNA大鼠相比,HF+PI3K shRNA大鼠的RVLM、PVN中PI3K的蛋白表达以及TNF-α、IL-1β和AT1aR的mRNA表达均显著降低(P<0.05)。超声心动图检查显示,HF+Con shRNA大鼠的LVEDV较基线时进一步增加(P<0.05),但HF+PI3K shRNA大鼠中没有显著增加。HE染色结果显示,HF+PI3K shRNA组神经元及神经纤维结构基本清晰,细胞肿胀不明显。此外,HF+PI3K shRNA组的右心室质量/体质量比和湿肺质量/体质量比明显低于HF+Con shRNA组(P<0.05)。血液动力学研究显示,HF+PI3K shRNA大鼠的LVEDP和LVDP/DTmax明显高于HF+Con shRNA大鼠(P<0.05)。结论:RVLM中PI3K信号的敲低减轻了HF大鼠PVN的神经炎症。Objective: To investigate the effects of PI3 K gene silencing in the rostral ventrolateral medulla(RVLM) on the neuroinflammation of the hypoventricular nucleus(PVN) in rats with heart failure(HF). Methods: Male rats received an RVLM microinjection of PI3 K shRNA or Con shRNA. One week later, some rats were euthanized to confirm the transfection potential and knockout efficiency of shRNA. The remaining rats underwent coronary artery ligation to induce HF or sham surgery. Results: Four weeks after coronary artery ligation, the expression of PI3 K protein and the mRNA expression of TNF-α, IL-1β and AT1 aR in both RVLM and PVN in HF+PI3 K shRNA rats were significantly lower than those in HF+Con shRNA rats(P<0.05). Echocardiography showed that LVEDV had increased further from baseline in HF+Con shRNA rats(P<0.05), but not in the HF+PI3 K shRNA rats though a non-significant trend in that direction was observed. The result of HE staining showed that the structure of neurons and nerve fibers in HF PI3 K shRNA group was clear and the swelling of cells was not obvious.In addition, the right ventricular weight/body weight ratio and wet lung weight/body weight ratio of the HF+PI3 K shRNA group were significantly lower than those of the HF+Con shRNA group(P<0.05). Hemodynamic studies showed that LVEDP and LVDP/DTmax were significantly higher in HF+PI3 K shRNA rats than in HF+Con shRNA rats(P<0.05). Conclusions: The knockdown of the PI3 K signal in RVLM can reduce the neuroinflammation of PVN in HF.

关 键 词：心力衰竭 磷脂酰肌醇3激酶 延髓腹外侧区 下丘脑室旁核 神经炎症 

分 类 号：R54[医药卫生—心血管疾病]