目的 探討燈盞花素對糖尿病大鼠心肌缺血再灌注損傷（MIRI）及線粒體自噬途徑的影響。方法 采用高糖高脂飲食聯(lián)合鏈脲佐菌素制備糖尿病模型，糖尿病模型成功后再制備MIRI模型，具體分組為對照組（不做任何處理）、模型組（糖尿病+MIRI）、假手術(shù)組（糖尿?。?，均ip等體積生理鹽水；燈盞花素低、高劑量組（糖尿病+MIRI），分別ip 100、200 mg/kg燈盞花素，每組各10只。連續(xù)給藥14 d后，全自動血生化儀檢測各組大鼠血清總膽固醇（TC）、三酰甘油（TG）、高密度脂蛋白膽固醇（HDL-C）、低密度脂蛋白膽固醇（LDL-C）水平變化，ELISA法檢測各組大鼠血清中炎性因子白細胞介素-1β（IL-1β）、IL-6、腫瘤壞死因子α（TNF-α）含量，采用超聲檢測各組大鼠心臟功能變化，HE染色觀察各組大鼠心肌組織病理變化，Western blotting檢測各組大鼠心肌組織微管相關(guān)蛋白輕鏈3（LC3）、Beclin1、哺乳動物雷帕霉素靶蛋白（mTOR）、磷酸肌醇3-激酶（PI3K）、p-PI3K、蛋白激酶B（Akt）和p-Akt蛋白表達情況。結(jié)果 與對照組相比，假手術(shù)組、模型組大鼠心肌細胞破碎、壞死，細胞排列不規(guī)則，心肌纖維斷裂，伴有炎性細胞浸潤，大鼠FBG、血清TC、TG、LDL-C水平、心率（HR）、左心室舒張末壓（LVEDP），心肌組織LC3-II/LC3-I、Beclin1蛋白表達及血清IL-1β、IL-6、TNF-α水平顯著升高（P<0.05），血清HDL-C水平、左心室收縮壓（LVSP）、平均動脈壓（MAP）和左室射血分數(shù)（LVEF）及心肌組織mTOR、p-PI3K/PI3K、p-Akt/Akt蛋白表達顯著降低（P<0.05）；與模型組相比，燈盞花素低、高劑量組大鼠損傷心肌細胞減少，細胞形態(tài)逐漸恢復(fù)正常，血清TC、TG、LDL-C水平、HR、LVEDP及心肌組織LC3-II/LC3-I、Beclin1蛋白表達及血清IL-1β、IL-6、TNF-α水平依次降低（P<0.05），血清HDL-C水平、LVSP、MAP、LVEF及心肌組織mTOR、p-PI3K/PI3K、p-Akt/Akt蛋白表達依次升高（P<0.05）。結(jié)論 燈盞花素可保護糖尿病MIRI大鼠心肌組織，減輕組織自噬及炎癥水平，可能是通過激活線粒體自噬PI3K/Akt/mTOR通路實現(xiàn)的。

Objective To investigate the effects of breviscapine on myocardial ischemia-reperfusion injury (MIRI) and mitochondrial autophagy pathway in diabetic rats. Methods Diabetes model was established by high sugar and high fat diet combined with streptozotocin. MIRI model was established after the success of diabetes model. The rats were randomly divided into control group (without any treatment), model group (diabetes + MIRI) and sham operation group (diabetes), all of which were intraperitoneally injected with equal volume normal saline; low and high dose breviscapine groups (diabetes + MIRI) were intraperitoneally injected with 100 and 200 mg/kg breviscapine respectively, with 10 rats in each group. After 14 days of continuous administration, the changes of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were detected by automatic blood biochemical instrument, the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in serum were detected by ELISA, the changes of cardiac function were detected by ultrasound, HE staining was used to observe the myocardial pathological changes, and Western blotting was used to detect the expressions of microtubule-associated protein light chain 3 (LC3), Beclin 1, mammalian target of rapamycin (mTOR), phosphoinositide 3-kinase (PI3K), p-PI3K, protein kinase B (Akt) and p-Akt protein. Results Compared with the control group, the myocardial cells of sham operation group and model group were broken and necrotic, cell arrangement was irregular, myocardial fibers were broken accompanied by inflammatory cell infiltration, FBG, serum TC, TG, LDL-C levels, heart rate (HR), left ventricular end diastolic pressure (LVEDP), LC3-II/LC3-I, Beclin1 protein expression in myocardial tissue, and serum IL-1, IL-6, TNF-α level was significantly increased (P<0.05), serum HDL-C level, left ventricular systolic pressure (LVSP), mean arterial pressure (MAP), left ventricular ejection fraction (LVEF) and mTOR, p-PI3K/PI3K, p-Akt/Akt protein expression in myocardial tissue were significantly decreased (P<0.05). Compared with the model group, the number of injured cardiomyocytes in breviscapine low-dose and high-dose groups decreased, and the cell morphology gradually returned to normal. TC, TG, LDL-C levels in serum, HR, LVEDP, LC3-II/LC3-I, Beclin1 protein expression in myocardial tissue and levels of IL-1β, IL-6, and TNF-α in serum were decreased sequentially (P<0.05), and the level of HDL-C in serum, LVSP, MAP, LVEF, and mTOR, p-PI3K/PI3K, and p-Akt/Akt protein expression in myocardial tissue were increased significantly (P<0.05). Conclusion Breviscapine can protect the myocardial tissue of diabetic rats with MIRI, and reduce the levels of autophagy and inflammation, which may be achieved by activating the mitochondrial autophagy PI3K/Akt/mTOR pathway.

R285.5

河南省科技攻關(guān)項目（182102310089）