Clinical Colloge of Wannan Medical College.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2021 Jun 25;50(3):352-360. doi: 10.3724/zdxbyxb-2021-0164.
To investigate the effects of salt-inducible kinase 2 (SIK2) on energy metabolism in rats with cerebral ischemia-reperfusion. Adult SD male rats were divided into 5 groups: sham group, ischemia group, reperfusion group, adenovirus no-load group, and SIK2 overexpression group with 5 animals in each group. The middle cerebral artery occlusion (MCAO) was induced with the modified Zea-Longa line thrombus method to establish the cerebral ischemia reperfusion model. Eight days before the MCAO, SIK2 overexpression was induced by injecting 7 μL adenovirus in the right ventricle, then MCAO was performed for followed by reperfusion HE staining was used to observe the pathological changes of cerebral tissue in rats; TTC staining was used to observe the volume of cerebral infarct. The levels of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) in rat brain tissue were detected by ELISA; the levels of SIK2 and hypoxia-inducible factor 1α (HIF-1α) in the rat brain tissues were detected by RT-qPCR and Western blotting. Compared with the sham group, SIK2 level was decreased in the ischemia group, and it was further declined in the reperfusion group (<0.05). Compared with the sham group and ischemic group, the pathological injury in reperfusion group were more severe, and the infarct size was larger; compared with the reperfusion group and adenovirus no-load group, the pathological injury of the SIK2 overexpression group was milder, and the infarct size is less. Compared with the sharn group, HIF-1α was increased in both ischemia group and reperfusion group, especially in ischemia group (all <0.05); HIF-1α level in the SIK2 overexpression group was higher than that in the reperfusion group and adenovirus no-load group (all <0.05). ATP level in ischemia group and reperfusion group was lower than that in the sham group, and the reperfusion group decreased more significantly than the ischemia group (<0.05); ADP content was increased in the ischemia and reperfusion group, and the ADP content in reperfusion group was significantly higher than that in the ischemia group (<0.05). ATP level in the SIK2 overexpression group was higher than that in the reperfusion group and adenovirus no-load group (all <0.05), and ADP was decreased in the SIK2 overexpression group (all <0.05). SIK2 can up-regulate the ATP level and down-regulate the ADP level in rat brain tissue and alleviate cerebral ischemia-reperfusion injury by increase the level of HIF-1α.
探讨盐诱导激酶 2（SIK2）对脑缺血再灌注大鼠能量代谢的影响。
成年雄性 SD 大鼠分为 5 组：假手术组、缺血组、再灌注组、空载腺病毒组和 SIK2 过表达组，每组 5 只。采用改良 Zea-Longa 线栓法诱导大脑中动脉闭塞（MCAO）建立脑缺血再灌注模型。在 MCAO 前 8 天，通过向右侧心室注射 7 μL 腺病毒诱导 SIK2 过表达，然后进行 MCAO 及随后的再灌注。HE 染色观察大鼠脑组织的病理变化；TTC 染色观察脑梗死体积。采用 ELISA 法检测大鼠脑组织中三磷酸腺苷（ATP）和二磷酸腺苷（ADP）水平；采用 RT-qPCR 和 Western blot 法检测大鼠脑组织中 SIK2 和低氧诱导因子 1α（HIF-1α）水平。
与假手术组相比，缺血组 SIK2 水平降低，再灌注组进一步降低（P<0.05）。与假手术组和缺血组相比，再灌注组病理损伤更严重，梗死体积更大；与再灌注组和空载腺病毒组相比，SIK2 过表达组的病理损伤较轻，梗死体积较小。与假手术组相比，缺血组和再灌注组 HIF-1α 升高，尤其在缺血组更为明显（均 P<0.05）；SIK2 过表达组 HIF-1α 水平高于再灌注组和空载腺病毒组（均 P<0.05）。与假手术组相比，缺血组和再灌注组 ATP 水平降低，再灌注组降低更为明显（P<0.05）；缺血组和再灌注组 ADP 含量增加，再灌注组 ADP 含量明显高于缺血组（均 P<0.05）。与再灌注组和空载腺病毒组相比，SIK2 过表达组 ATP 水平升高（均 P<0.05），ADP 降低（均 P<0.05）。
SIK2 可通过上调 HIF-1α 水平增加大鼠脑组织中 ATP 水平，降低 ADP 水平，减轻脑缺血再灌注损伤。
