室旁核硫化氢对高盐诱导高血压模型大鼠PI3K/Akt通路及血压的影响  

Effects of hydrogen sulfide in paraventricular nuclei on PI3K/Akt pathway and blood pressure in high salt-induced hypertensive rats

作　　者：张东东[1,2] 谷青芸 尤清欣 金颖新 张嘉倪 王浩然 王凤月 陈淑月 苏嘉璐 梁衍锋[1,2] Zhang Dongdong;Gu Qingyun;You Qingxin;Jin Yingxin;Zhang Jiani;Wang Haoran;Wang Fengyue;Chen Shuyue;Su Jialu;Liang Yanfeng(School of Basic Medicine,Jiamusi University,Jiamusi 154007,Heilongjiang Province,China;Key Laboratory of Microecology-Immune Regulation Network and Related Diseases,Jiamusi University,Jiamusi 154007,Heilongjiang Province,China)

机构地区：[1]佳木斯大学基础医学院,黑龙江省佳木斯市154007 [2]佳木斯大学微生态-免疫调节网络与相关疾病重点实验室,黑龙江省佳木斯市154007

出　　处：《中国组织工程研究》2023年第26期4168-4174,共7页Chinese Journal of Tissue Engineering Research

基　　金：黑龙江省自然科学基金项目(LH2021H103),项目负责人:梁衍锋;黑龙江省省属高等学校基本科研业务费项目(2019-KYYWF-1339),项目负责人:梁衍锋;黑龙江省大学生创新创业训练计划项目(202010222056),项目负责人:张嘉倪。

摘　　要：背景:室旁核是心血管调节中枢,其对外周交感神经和血压的调控起着重要作用。硫化氢(H2S)作为一种新型气体信号分子,具有抗炎、抗氧化等作用,其合成酶在室旁核存在表达,其在高血压的作用机制仍需进一步研究。目的:研究室旁核H2S对高盐诱导的高血压大鼠血压、外周交感神经活动及室旁核PI3K/Akt通路的影响,探讨其在高血压中的作用及中枢机制。方法:雄性Dahl盐敏感性大鼠40只,随机分为4组:正常对照组、正常干预组、高盐模型组和高盐干预组,2个高盐组大鼠给予高盐饲料喂养4周,每周用尾动脉血压测量仪监测大鼠血压。4周后,干预组大鼠双侧室旁核通过微型渗透泵持续注射H2S缓释剂GYY4137,正常对照组和高盐模型组均给予等量人工脑脊液。干预6周后取材,ELISA法检测血浆去甲肾上腺素和室旁核H2S水平,Western blot、免疫组化法检测室旁核中的PI3K-p85、p-Akt和t-Akt的蛋白表达。结果与结论:①与正常对照组相比,高盐模型组的平均动脉压、血浆去甲肾上腺素水平明显升高(P<0.01);与高盐模型组相比,高盐干预组平均动脉压、去甲肾上腺素水平明显下降(P<0.01);②与正常对照组相比,高盐模型组室旁核中PI3K-p85和p-Akt的蛋白表达明显升高(P<0.01);与高盐模型组相比,高盐干预组室旁核中PI3K-p85和p-Akt的蛋白表达明显下降(P<0.01);③以上结果表明,室旁核H2S在高盐诱导的高血压中具有抑制外周交感神经活动、降低血压的作用,其在降低血压时可明显抑制室旁核PI3K/Akt通路,这将为高血压的临床治疗寻找新的靶点,并为新药开发奠定了理论基础。BACKGROUND:The paraventricular nucleus is the center of cardiovascular regulation,which plays an important role in the regulation of peripheral sympathetic nerves and blood pressure.As a new type of gas signal molecular,hydrogen sulfide has anti-inflammatory and anti-oxidation effects.And the synthetase of hydrogen sulfide is expressed in the paraventricular nucleus.The mechanism of hydrogen sulfide in hypertension needs to be studied.OBJECTIVE:To study the effects of hydrogen sulfide in the paraventricular nucleus on blood pressure,peripheral sympathetic nerve activity and PI3K/Akt pathway in high salt-induced hypertensive rats and to explore the mechanism of hydrogen sulfide in hypertension.METHODS:Forty male Dahl rats were randomly divided into four groups:normal control group,normal intervention group,high-salt model group and highsalt intervention group.The rats in the two high-salt groups were fed high-salt diet for 4 weeks.The blood pressure of each rat was monitored by the caudal artery every week.After 4 weeks,the rats in the intervention groups were injected with GYY4137 in the bilateral paraventricular hypothalamic nucleus through a micro osmotic pump.Rats in the normal control group and the high-salt model group were given the same amount of artificial cerebrospinal fluid.After 6 weeks,the levels of plasma norepinephrine and hydrogen sulfide in the paraventricular nucleus were detected by ELISA,and the expressions of PI3K-p85,p-Akt and t-Akt in the paraventricular nucleus were detected by western blot and immunohistochemistry.RESULTS AND CONCLUSION:Compared with the normal control group,the levels of mean arterial pressure and plasma norepinephrine were significantly increased in the high-salt model group(P<0.01).Compared with the high-salt model group,the levels of mean arterial pressure and plasma norepinephrine were significantly decreased in the high-salt intervention group(P<0.01).Compared with the normal control group,the expressions of PI3K-P85 and p-Akt in the paraventricular nucleus were sign

关 键 词：硫化氢 高血压 室旁核 PI3K/AKT通路 去甲状腺素 模型 大鼠 

分 类 号：R446[医药卫生—诊断学] R318[医药卫生—临床医学] R496