摘要
目的观察自噬机制是否参与慢性间歇低氧诱导大鼠心肌肥厚形成过程、白藜芦醇是否通过调节自噬水平改变慢性间歇低氧大鼠心肌肥厚程度，并探讨慢性间歇低氧以及白藜芦醇诱导自噬的相关信号通路。方法SD大鼠随机分4组，每组8只，分别为（1）对照组（CON）：常氧环境健康对照组；（2）慢性间歇低氧组（CIH）：大鼠间歇低氧干预；（3）慢性间歇低氧干预同时予白藜芦醇（RSV）灌胃组（CIH＋RSV组）；（4）慢性间歇低氧干预同时予白藜芦醇灌胃以及氯喹（Cq）腹腔注射组（CIH＋RSV＋Cq组）。7周后Westernblot技术检测微管相关蛋白1轻链3（LC3）、Beelin、P62、心房利钠肽（ANP）、B肌球蛋白重链（9-MHC）、腺苷酸活化蛋白激酶（AMPK）、磷酸化腺苷酸活化蛋白激酶（P—AMPK）、哺乳动物西罗莫司靶蛋白（mTOR）、磷酸化哺乳动物西罗莫司靶蛋白（P—roTOR）、裂解的半胱氨酸天冬氨酸蛋白酶3（cleaved caspase3）的表达量；HE染色计算心肌横截面积；天狼星红染色计算心肌组织胶原面积百分比。结果在CON、CIH、CIH＋RSV3组大鼠中，LC31I／LC3I比值、Beclin蛋白表达量呈递增趋势、P62蛋白表达量呈递减趋势，氯喹注射抑制大鼠自噬，可观察到LC3 Ⅱ／LC3Ⅰ蛋白相对比值较cIH＋RSV组升高（均P〈0．05）；与c0N组比较，大鼠心肌横截面积、胶原面积百分比、蛋白ANP、B—MHC、Cleavedcaspase3表达量升高，白藜芦醇干预后，上述指标均有改善，而较CIH＋RSV组，上述指标在CIH＋RSV＋Cq组中升高，以上各组所有指标差异均有统计学意义（均P〈0．05）；在CON组、CIH组、CIH＋RSV组中，PAMPK蛋白表达量递增，而P—mTOR蛋白表达量依次递减，各组磷酸化蛋白表达量差异均有统计学意义（均P〈0．05），AMPK、mTOR蛋白表达量在3组中的变化差异无统计学意义。结论慢性间歇低氧通过诱导自�
Objective To examine whether autophagy plays a role in the development of chronic intermittent hypoxia-induced cardiac hypertrophy, whether resveratrol can reverse the process by modulating autophagy and what molecular pathways are involved. Methods Rats were randomly divided into four groups. Eight rats were treated with normoxia （control group） ,eight were exposed to chronic intermittent hypoxia （CIH） （CIH group）,eight were exposed to CIH plus resveratrol （RSV） （CIHq-RSV group） and eight were exposed to CIH, RSV and chloroquine （Cq） （CIH q-RSVq-Cq group）. After treatment for seven weeks, the levels of LC3, Beclin, P62, ANP, β-MHC, AMPK, P- AMPK, mTOR, P-mTOR and eleaved-easpase 3 were detected by Western blot. The area of cardiomyocytes and the ratio of hrotic area to the total area were obtained by HE and Sirius Red staining. Results Rats in the CIH＋RSV group were associated with an increased ratio of LC3 Ⅱ / LC3 Ⅰ ,increased Beclin levels and decreased P62 levels, compared with those in the control and CIH groups （all P〈0.05）. After chloroquine injection, the ratio of LC3 Ⅱ/LC3 Ⅰ was markedly increased in the CIH＋RSV＋Cq group,compared with that in the CIH＋RSV group （all P〈0.05）. Moreover, the CIH group was associated with significantly increased area of cardiomyocytes,ratio of fibrotic area to the total area,and levels of ANP,β-MHC and cleaved-easpase 3, compared with the control group （all P〈0.05）. However,their values markedly decreased in the CIH＋RSV group and significantly increased in the CIH ＋ RSV ＋ Cq group, compared with the CIH group （all P〈 0.05）. Furthermore, there were tendencies of progressively increased levels of P-AMPK and decreased levels of P-roTOR among the control group, CIH group and CIH ＋ RSV group （both P〈0.05）. However, levels of AMPK and roTOR were similar among the three groups （P 〉 0.05 ）. Conclusions Chronic intermittent hypoxia and resveratrol can affect the level of cardiac hypertrophy by au
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2017年第12期1356-1361,共6页
Chinese Journal of Geriatrics
基金
国家自然科学基金（81370182）
关键词
睡眠呼吸暂停
阻塞性
心肌病
肥厚性
自噬
Sleep apnea, obstructive
Cardiomyopathy, hypertrophic
Autophagy
