白藜芦醇调控Sirt1减轻糖尿病心肌缺血再灌注后急性肺损伤相关内质网应激  

Resveratrol regulates Sirt1 to reduce endoplasmic reticulum stress in acute lung injury induced by myocardial ischemia reperfusion in diabetic rats

作　　者：陈婷婷[1] 吐尔逊阿依·买买提 陈思宇[1] 李爱梅[1] CHEN Tingting;Tuerxunayi·Maimaiti;CHEN Siyu;LI Aimei(Deparement of Anesthesiology,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆医科大学第一附属医院麻醉科,新疆乌鲁木齐830011

出　　处：《陕西中医》2022年第4期437-441,共5页Shaanxi Journal of Traditional Chinese Medicine

基　　金：新疆维吾尔自治区自然科学基金资助项目(2019D01C298)。

摘　　要：目的:探讨白藜芦醇(RSV)预处理对糖尿病大鼠心肌缺血再灌注(IR)继发急性肺损伤(ALI)的保护机制及其对内质网应激(ERS)的影响。方法:通过腹腔注射链脲佐菌素诱导2型糖尿病大鼠模型,选取32只糖尿病造模成功大鼠,随机分为假手术组(DS组)、缺血再灌注模型组(DIR组)、白藜芦醇低剂量组(RLIR组)、白藜芦醇高剂量组(RHIR组)。采用结扎左冠状动脉前降支30 min后再灌注2 h诱导MIR继发ALI模型。RLIR组于缺血前15 min及再灌注前1 min从尾静脉注射RSV 10 mg/kg(采用0.9%氯化钠水溶液稀释),RHIR组于缺血前15 min及再灌注前1 min尾静脉注射RSV 20 mg/kg。于再灌注2 h时放血处死大鼠,收集动脉血测量氧分压及血清炎症因子,收集肺组织测量湿干重比值(W/D),观察光镜下肺组织病理学变化,采用Western blot法检测肺组织Sirt1、GRP78及CHOP的表达。结果:与DS组比较,DIR组大鼠肺组织病理损伤严重,肺W/D值增加、动脉血氧分压降低,血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平增加,血清白细胞介素-4(IL-4)降低,肺组织Sirt1水平降低,GRP78及CHOP的表达增高,差异有统计学意义(P<0.05)。与DIR组比较,RHIR组肺组织组织病理学损伤减轻,肺W/D值降低,动脉血氧分压升高,血清IL-6、TNF-α水平降低,差异有统计学意义(P<0.05),IL-4水平升高,肺组织Sirt1水平升高,GRP78及CHOP的表达降低。而RLIR组上述表现与IR组比较差异无统计学意义(P>0.05)。结论:白藜芦醇预处理可通过升高Sirt1减轻大鼠糖尿病心肌IR继发性ALI,机制可能与其抑制肺组织内质网应激蛋白活性有关。Objective:To investigate the protective mechanism of resveratrol(RSV)preconditioning on acute lung injury(ALI)secondary to myocardial ischemia-reperfusion(IR)in diabetic rats and its effect on endoplasmic reticulum stress(ERS).Methods:32 diabetic rats were randomly divided into sham operation group(DS),ischemia-reperfusion model group(DIR),low-dose resveratrol group(RLIR),and high-dose resveratrol group(RHIR).Model of acute lung injury secondary to myocardial ischemia-reperfusion was induced by reperfusion for 2 h after ligation of the anterior descending branch of the left coronary artery for 30 min.RLIR group was injected with RSV 10 mg/kg via tail vein(diluted with normal saline)15 min before ischemia and 1 min before reperfusion,while RHIR group was injected with RSV 20 mg/kg via tail vein 15 min before ischemia and 1min before reperfusion.At 2 h of reperfusion,the rats were sacrificed by bloodlet.Arterial blood was collected to measure oxygen partial pressure and serum inflammatory factors,and lung tissue was collected to measure the ratio of wet and dry weight(W/D).Lung histopathological changes were observed under light microscope,and the expressions of Sirt1,GRP78 and CHOP in lung tissue were detected by Western blot.Results:Compared with the DS group,the lung tissues of the rats in the DIR group were severely damaged,including increased W/D value,decreased arterial oxygen partial pressure,increased IL-6,TNF-αand decreased IL-4 in serum,decreased Sirt1,and increased GRP78 and CHOP in lung tissue.Compared with DIR group,histopathological injury in lung tissue of the RHIR group was reduced,lung W/D value was reduced,arterial oxygen partial pressure was increased,serum IL-6 and TNF-αwas decreased,the IL-4 was increased,Sirt1 level in lung tissue was increased,while the GRP78 and CHOP were decreased.However,there was no significant difference between RLIR group and IR group.Conclusion:Resveratrol preconditioning can alleviate acute lung injury induced by myocardial ischemia reperfusion in diabetic rats by i

关 键 词：糖尿病心肌缺血 急性肺损伤 白藜芦醇 内质网应激 肺W/D值 白细胞介素-6 动脉血氧分压 肿瘤坏死因子-α 大鼠 

分 类 号：R587.2[医药卫生—内分泌]