瘦素通过减轻氧化应激和随后的神经元凋亡来减轻小鼠的缺血性脑损伤。

Leptin administration alleviates ischemic brain injury in mice by reducing oxidative stress and subsequent neuronal apoptosis.

机构信息

Research Laboratory of Biochemistry, Basic Medical Institute, Basic Medical Institute, Chinese General Hospital of PLA, 28 Fuxing Road, Beijing 100853, People's Republic China.

出版信息

J Trauma Acute Care Surg. 2012 Apr;72(4):982-91. doi: 10.1097/TA.0b013e3182405459.

DOI:10.1097/TA.0b013e3182405459

PMID:22491615

Abstract

BACKGROUND

Recent research has indicates that leptin plays a protective role in traumatic brain injury. We studied the protective effect of leptin on cerebral ischemia/reperfusion injury by using mice transient focal cerebral ischemia/reperfusion injury model.

METHODS

The distribution of 125I-leptin in the mouse brain was assessed by radioimmunoassay method. Mouse models of transient focal cerebral ischemia were established by occlusion of the right middle cerebral artery for two hours followed by 24 hours reperfusion. The neurologic deficits and infarct volume were determined using the Longa's score and 2,3,5-triphenyltetrazolium chloride staining, respectively. Regional cerebral blood flow was monitored by a laser-Doppler blood flowmeter. The levels of malondialdehyde, nitric oxide, nitric oxide synthase, and superoxide dismutase were detected according to respective assay kit. The histologic changes and neuronal apoptosis were observed with hematoxylin and eosin and transferase-mediated dUTP-biotin nick end labeling staining, respectively. The expression of B-cell lymphoma/leukemia-2 (Bcl-2) and cysteineasparateprotease-3 (caspase-3) were investigated by Western blot and real-time polymerase chain reaction assay.

RESULTS

Leptin decreased infarct volume and neurologic defects and improved regional cerebral blood flow and microvascular branch blood flow after injury. The malondialdehyde and nitric oxide levels were reduced, and superoxide dismutase level was increased after leptin treatment, which also minimized histologic changes and neuronal apoptosis, led to the upregulation of Bcl-2 and downregulation of caspase-3 expression after injury.

CONCLUSIONS

Peripherally administered leptin crossed the blood-brain barrier and was distributed into multiple regions of the brain; in the brain, leptin directly alleviated the injury-evoked damages by reducing oxidative stress and neuronal apoptosis.

摘要

背景

最近的研究表明，瘦素在创伤性脑损伤中发挥保护作用。我们通过使用小鼠短暂性局灶性脑缺血再灌注损伤模型，研究了瘦素对脑缺血再灌注损伤的保护作用。

方法

通过放射免疫法评估 125I-瘦素在小鼠脑中的分布。通过阻断右侧大脑中动脉 2 小时，然后再灌注 24 小时，建立小鼠短暂性局灶性脑缺血模型。使用 Longa 评分和 2,3,5-三苯基氯化四氮唑染色分别确定神经功能缺损和梗死体积。通过激光多普勒血流计监测局部脑血流。根据各自的测定试剂盒检测丙二醛、一氧化氮、一氧化氮合酶和超氧化物歧化酶的水平。用苏木精和伊红和转移酶介导的 dUTP-生物素缺口末端标记染色分别观察组织学变化和神经元凋亡。通过 Western blot 和实时聚合酶链反应检测 B 细胞淋巴瘤/白血病-2 (Bcl-2) 和半胱氨酸天冬氨酸蛋白酶-3 (caspase-3) 的表达。