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[目的]观察川芎嗪干预肝缺血再灌注损伤大鼠P-选择素表达,探索可能的病理机制,为预防治疗肝细胞缺血再灌注损伤提供依据。[方法]将64只SD大鼠随机分为4组,肉眼观察肝脏形态变化,光镜、电镜观察肝细胞形态变化,免疫组化SABC法检测肝组织中P-选择素表达。[结果]缺血再灌注组可见肝细胞水肿明显,伴空泡形成,间质充血水肿及炎性细胞浸润,再灌注6 h可见肝组织出现明显的点状坏死灶,并可见到灶性坏死;再灌注24 h肝组织可见多发性灶性坏死及片状坏死灶。川芎嗪干预组各时间点肝组织外观与正常肝相似,光镜下肝细胞无明显肿胀,有极少量空泡形成,但无变性或坏死,且间质无明显变化。免疫组化SABC法检测显示,缺血再灌注早期P-选择素即在肝组织中表达,与川芎嗪干预组及假手术组比较,差异有统计学意义(P<0.01)。缺血再灌注组P-选择素表达以1 h时最为明显,与再灌6 h及24 h相比,差异有统计学意义(P<0.01)。[结论]川芎嗪能有效抑制P-选择素的表达,减轻肝缺血再灌注损伤。P-选择素主要在缺血再灌注损伤早期表达。P-选择素介导中性粒细胞滚动黏附,可能是肝缺血再灌注损伤的主要机制之一。
[Objective] To observe the effects of tetramethylpyrazine on the expression of P-selectin in rats with hepatic ischemia reperfusion injury and explore the possible pathological mechanism, so as to provide basis for the prevention and treatment of hepatocytes ischemia-reperfusion injury. [Methods] Sixty-four SD rats were randomly divided into 4 groups. Morphological changes of the liver were observed with naked eyes. Morphological changes of hepatocytes were observed by light and electron microscopy. Expression of P-selectin in liver tissues was detected by immunohistochemical SABC method. [Results] The hepatocyte edema was obvious in the ischemia-reperfusion group, accompanied by vacuolization, interstitial hyperemia and edema, and inflammatory cell infiltration. After 6 hours of reperfusion, obvious focal necrotic lesions appeared in the liver tissue, and focal necrosis was visible. ; reperfusion 24 h liver tissue showed multiple focal necrosis and flaky necrosis. The appearance of liver tissue was similar to that of normal liver at each time point in the tetramethylpyrazine intervention group. There was no obvious swelling of the hepatocytes under light microscope, but there was very little vacuolization, but no degeneration or necrosis, and there was no significant change in the interstitial substance. Immunohistochemical SABC assay showed that P-selectin was expressed in liver tissue at the early stage of ischemia-reperfusion, and the difference was statistically significant (P<0.01) compared with the tetramethylpyrazine intervention group and the sham operation group. The expression of P-selectin in ischemia-reperfusion group was the most obvious at 1 h, and there was a significant difference compared with that at 6 h and 24 h after reperfusion (P<0.01). [Conclusion] Tetramethylpyrazine can effectively inhibit the expression of P-selectin and reduce hepatic ischemia-reperfusion injury. P-selectin is mainly expressed in the early stage of ischemia-reperfusion injury. P-selectin mediates neutrophil rolling adhesion and may be one of the main mechanisms of hepatic ischemia-reperfusion injury.