自噬在X射线照射所致心肌线粒体损伤中的作用

目的观察X射线照射对大鼠心肌线粒体功能的影响以及自噬在线粒体功能损伤中的作用。方法将135只实验大鼠分成假照射组（10只）、照射组（80只）和照射＋3．甲基腺嘌呤（3-MA）组（45只），假照射组接受0GyX射线照射，照射组给予20Gyx射线照射，照射＋3-MA组接受20Gvx射线照射前30min腹腔注射2μl 3-MA。采用蛋白免疫印迹法和实时定量PCR法检测心肌细胞的LC3II及Beclin1蛋白表达及其mRNA水平变化，检测左心室舒张压及＋-dP／dtmax（左心室压力上升及下降的最大速率）等离体心功能指标。结果与假照射组相比，照射组大鼠经20GyX射线照射后离体心功能在21d时出现降低；而在1d时心肌组织线粒体功能便出现了损伤；同时，心肌细胞自噬水平在3h、6h、12h、1d、2d、4d及7d时出现明显上升，与假照射组之间的差异显著，且在6h达到最高值。与照射组相比，照射＋3一MA组大鼠心肌LC3II及Beclin1表达水平明显下降，且心功能出现异常的时间提前至14d。结论x射线照射损伤大鼠心肌线粒体功能并诱导自噬发生，可能是心肌保护的重要因素。

Effects of autophagy in myocardial mitochondrial injury caused by X-ray irradiation

Objective To observed the effects of X-ray irradiation on myocardial mitochondrial function and role of autophagy in mitochondrial injury. Methods The rats were divided into sham- irradiation control group, irradiation group and irradiation＋3-methyladenine（3-MA） group. Rat in sham- irradiation control group accepted no irradiation, while rat in irradiation group accepted local 20 Gy X-ray irradiation in the chest, the last group accepted 20 Gy X-ray irradiation prior to intraperitoneal injection 2 Ix1 3-MA. Western blot and real time PCR were used to detect the expression of LC3 ]] and Beclin 1 in protein and their mRNA levels. In vitro cardiac function was used to detect the changes of the left ventricular diastolic pressure （LVDP）, the maximal rate of rise of pressure in the isovolumetric systolic left ventricle （＋dP/dt~）and the maximal rate of rise of pressure in the isovolumetric diastolic left ventricle （-dP/ dt~ ）. Results Compared with the sham-irradiation control group, there were the decreased of the LVDP, ＋dP/dt~ and -dP/dt~ at 21 d, and myocardial mitochondrial injury at 1 d after 20 Gy irradiation. The expression of LC3 and Beclin 1 in protein and mRNA levels increased significantly at 3 h, 6 h, 12 h, 1 d, 2 d, 4 d and 7 d after 20 G y irradiation, up to peak at 6 h. Compared with irradiation group, intraperitoneal injection 2 p2 3-MA 30 min before irradiation, the expression of LC3 1I and Beclin 1 in protein decreased significantly at 6 h after irradiation, there were the decreased of the LVDP, ＋dP/dt~ and -dP/dtmax at 14 d, then the irradiation group for 21 days. Conclusion X-ray irradiation could injury myocardial mitochondrial function and induce autophagy in rat myocardial cell, which was an important factor of myocardial protection.