目的 探究紫花前胡素調(diào)節(jié)趨化因子配體2（CCL2）-CC基序趨化因子受體2（CCR2）信號通路對腦缺血再灌注大鼠的神經(jīng)保護(hù)作用。方法 將大鼠分為假手術(shù)組、模型組、紫花前胡素（10、25 mg/kg）組、紫花前胡素＋CCL2組、尼莫地平組，每組12只。除假手術(shù)組，其余大鼠均進(jìn)行大腦中動脈閉塞/再灌注（MCAO/R）造模。紫花前胡素組大鼠分別ip 10、25 mg/kg紫花前胡素（溶于生理鹽水）；紫花前胡素＋CCL2組大鼠ip 25 mg/kg紫花前胡素后，尾iv 1 µg CCL2重組蛋白；尼莫地平組大鼠ip 10.8 mg/g尼莫地平，其余組注射等量生理鹽水，1次/d，給藥7 d。給藥后，測定大鼠神經(jīng)學(xué)評分和腦水含量；TTC染色測定腦梗死體積；蘇木素–伊紅（HE）觀察腦組織變化；免疫熒光染色檢測腦組織緊密連接蛋白claudin-5表達(dá)；Western blotting檢測腦組織CCL2、CCR2蛋白表達(dá)。結(jié)果 與模型組比較，紫花前胡素組大鼠神經(jīng)學(xué)評分降低，腦水含量降低，腦梗死體積減少，腦組織水腫減輕，細(xì)胞形態(tài)改善，腦組織中claudin-5蛋白表達(dá)提高，CCL2、CCR2蛋白相對表達(dá)量降低（P＜0.05），且呈劑量相關(guān)性。與紫花前胡素組相比，紫花前胡素＋CCL2組大鼠腦組織損傷加重，紫花前胡素的神經(jīng)保護(hù)作用被逆轉(zhuǎn)（P＜0.05）。結(jié)論 紫花前胡素通過抑制CCL2-CCR2信號通路對腦缺血再灌注大鼠發(fā)揮神經(jīng)保護(hù)作用。

Objective To explore the neuroprotective effects of decursin on cerebral ischemia-reperfusion rats by regulating the CCL2-CCR2) signaling pathway. Methods Rats were divided into the sham operation group, the model group, the decursin (10 and 25 mg/kg) group, decursin + CCL2 group, and the nimodipine group, with 12 rats in each group. Except for the sham operation group, middle cerebral artery occlusion/reperfusion (MCAO/R) modeling was performed in the remaining rats. The rats in the decursin group were respectively treated with ip at 10 and 25 mg/kg of decursin (dissolved in 0.9% normal saline). In the decursin + CCL2 group of rats, after ip at 25 mg/kg of decursin, tail iv was 1 µg of CCL2 recombinant protein. Rats in the nimodipine group received ip at a dose of 10.8 mg/g of nimodipine, while the other groups were injected with the same amount of normal saline once a day for 7 days. After administration, the neurological score and brain water content of rats were measured. TTC staining was used to measure the volume of cerebral infarction. Hematoxylin-eosin (HE) was used to observe changes in brain tissue. Immunofluorescence staining was performed to measure the tight junction protein claudin-5 in brain tissue. In addition, Western blotting was used to measure the CCL2 and CCR2 proteins in brain tissue. Results Compared with the model group, decursin groups showed decreased neurological scores, decreased brain water content, reduced cerebral infarction volume, reduced brain tissue edema, improved cell morphology, increased claudin-5 protein in brain tissue, and decreased CCL2 and CCR2 proteins expression (P < 0.05),with a dose-dependent correlation. Compared with the decursin group, the decursin + CCL2 group showed aggravated brain tissue damage, and the neuroprotective effect of decursin was reversed (P < 0.05). Conclusion Decursin exerts neuroprotective effects on cerebral ischemia-reperfusion rats by inhibiting CCL2-CCR2 signaling pathway.

R285.5

南充市科技計劃項目（20YFZJ0025）