【罂粟摘要】右美托咪定抑制JNK通路减轻大鼠脑缺血再灌注损伤
右美托咪定抑制JNK通路减轻大鼠脑缺血再灌注损伤
翻译：任文鑫 编辑：佟睿 审校：曹莹
脑缺血再灌注损伤（CI/RI）是一种常见的脑血管疾病，其发病率高，致残率高，严重威胁人类健康。本研究旨在探讨右美托咪定（Dex）对CI/RI中c-Jun N末端激酶（JNK）通路的影响，并为脑缺血后脑功能的恢复提供理论依据。
SD大鼠24只，随机分为假手术组、假手术+地塞米松组、假手术+育亨宾+右美托咪定组和假手术+SP600125组；缺血再灌注组、I/R+地塞米松组、I/R+育亨宾+右美托咪定组和I/R+SP600125组，并采用线栓法建立局灶性脑缺血再灌注大鼠模型。测量神经功能缺损评分和梗死体积。用干/湿重比测定脑含水量，用2,3,5-三苯基四氮唑（TTC）染色法测定脑梗死体积。免疫荧光染色（IF）检测p-JNK和裂解半胱甘冬蛋白酶3的细胞分布，western blotting（WB）检测总JNK和p-JNK。
与假手术组相比，I/R+Dex、I/R+Yoh+Dex、I/R+SP600125组大鼠在不同程度上出现了左前肢偏瘫，神经功能缺损评分、脑含水量、梗死体积明显升高，裂解半胱甘冬蛋白酶3、p-JNK表达明显上调（p<0.05）。与I/R组相比，I/R + Dex、I/R + Yoh + Dex、I/R + SP600125组的神经功能缺损评分、脑水含量、梗死体积、裂解半胱甘冬蛋白酶3、p-JNK的表达均明显下降（P<0.05），与I/R + Dex组相比，I/R + Yoh + Dex组的神经功能缺损评分、脑含水量、梗塞体积和裂解半胱甘冬蛋白酶3、p-JNK的表达明显增加（P<0.05）。双重免疫荧光染色显示p-JNK和星形胶质细胞标志物GFAP之间有很强的共聚焦作用。
JNK信号通路参与了CI/RI。抑制JNK通路可阻断裂解半胱甘冬蛋白酶3的激活，从而降低CI/RI。Dex可以通过增加α2-肾上腺素受体和阻断JNK的磷酸化和裂解半胱甘冬蛋白酶3的激活来缓解大鼠的脑CI/RI。
Bingxiao Zhao, Da Li, Shuchi Zhang, Long He, Yanqiu Ai,Dexmedetomidine attenuates cerebral ischemia-reperfusion injury in rats by inhibiting the JNK pathway.Ann Palliat Med 2021;10(6):6768-6778
Dexmedetomidine attenuates cerebral ischemia-reperfusion injury
in rats by inhibiting the JNK pathway
Background: Cerebral ischemic reperfusion injury (CI/RI) is a common cerebrovascular disease with
high morbidity and disability that threatens human health. This study was conducted to explore the effects of dexmedetomidine (Dex) on the c-Jun N-terminal kinase (JNK) pathway in CI/RI, and to provide a theoretical basis for the recovery of brain function after cerebral ischemia.
Methods: Sprague Dawley (SD) rats (n=24) were randomly divided into Sham, Sham + Dex, Sham +
yohimbine (Yoh) + Dex, Sham + SP600125, ischemic reperfusion (I/R), I/R + Dex, I/R + Yoh + Dex, and I/R + SP600125 groups, and a focal cerebral ischemia reperfusion rat model was established by linear thrombus. The neurological deficit score and infarct volume were measured. Wet/dry weight ratios were used to measure brain water content, and cerebral infarct volume was determined by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The cellular distribution of p-JNK and cleaved caspase-3 were examined using immunofluorescent staining (IF) and the total JNK and p-JNK were determined by Western blotting (WB).
Results: Compared with the Sham group, the rats in I/R, I/R + Dex, I/R + Yoh + Dex, and I/R + SP600125
groups developed hemiparesis of the left forelimb at different levels with a higher neurological deficit score, brain water content, infarct volume, and markedly upregulated expression of cleaved caspase-3, p-JNK (P<0.05). Compared with the I/R group, the neurological deficit score, brain water content, infarct volume, and expression of cleaved caspase-3, p-JNK were markedly decreased in I/R + Dex, I/R + Yoh + Dex, and I/R + SP600125 groups (P<0.05), and compared with the I/R + Dex group, the neurological deficit score, brain water content, infarct volume, and expression of cleaved caspase-3, p-JNK were markedly increased in the I/R + Yoh + Dex group (P<0.05). Double immunofluorescence staining showed there was a strong colocalization between p-JNK and the astroglial marker GFAP.
Conclusions: The JNK signaling pathway is involved in CI/RI. Inhibition of the JNK pathway blocked
caspase-3 activation which can decrease CI/RI. Dex can alleviate cerebral CI/RI in rats by increasing α2-
adrenergic receptor and blocking JNK phosphorylation and activation of caspase-3.
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