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目的:观察川芎嗪微乳凝胶对肠粘连的防治效果,通过检测大鼠腹腔液细胞因子及粘连组织抗氧化酶进一步探讨其对肠粘连防治作用的机理。方法:取SD大鼠70只,随机分为7组:正常组、模型组、川芎嗪对照组、空白微乳凝胶组,川芎嗪微乳凝胶高、中、低剂量组,每组10只。除正常对照组外,其余各组大鼠均制备肠粘连模型。正常对照组和模型组ip生理盐水,川芎嗪对照组ip川芎嗪注射液(15 mg·kg-1·d-1),连续给药10 d。川芎嗪微乳凝胶低、中、高剂量组(7.5,15,30 mg·kg-1)在造模后,腹腔内以注射器均匀涂抹于创面,并按10 d量放大,一次性给药。各组大鼠于术后第11天处死,ELISA法测定腹腔液白介素-6(IL-6)、白介素-18(IL-18)和肿瘤坏死因子α(TNF-α)含量,并取粘连组织检测超氧化物歧化酶(SOD)、一氧化氮合酶(NOS)、还原型谷胱甘肽(GSH)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)活力及丙二醛(MDA)、一氧化氮(NO)含量,同时记录大鼠肠粘连级别。取粘连肠组织观察病理变化。结果:与正常组相比,模型组腹腔液IL-6,IL-18和TNF-α含量增高(P<0.01),粘连组织中MDA,NO,NOS活性增强(P<0.01),CAT,GPx,GSH,SOD的活性下降(P<0.01)。与模型组相比,川芎嗪微乳凝胶低、中、高剂量组的肠粘连程度明显减轻(P<0.05,P<0.01),病理显示肠粘连逐渐松解,腹腔液IL-6,IL-18和TNF-α含量明显降低(P<0.05,P<0.01),粘连组织中MDA,NO含量及NOS活性明显下降(P<0.05,P<0.01),CAT,GPx,GSH,SOD的活性增强(P<0.05,P<0.01)。结论:川芎嗪微乳凝胶可明显减轻肠粘连的程度,对肠粘连具有防治作用。其作用可能是通过下调IL-18的表达,进而使相关基因的表达下调,导致下游炎性因子TNF-α,IL-6等表达减少,同时与抗肠组织过氧化损伤有关。
OBJECTIVE: To observe the effect of ligustrazine microemulsion gel on the prevention and treatment of intestinal adhesion, and to explore the mechanism of prevention and treatment of intestinal adhesion by detecting the cytokines in peritoneal fluid and the anti-oxidative enzymes of adhesion tissue. Methods: Seventy SD rats were randomly divided into 7 groups: normal group, model group, ligustrazine control group, blank microemulsion gel group, ligustrazine microemulsion gel high, medium and low dose groups only. In addition to the normal control group, the rest of the rats were prepared intestinal adhesion model. Normal control group and model group ip saline, ligustrazine control group ip ligustrazine injection (15 mg · kg-1 · d-1), continuous administration of 10 d. Ligustrazine microemulsion gel low, medium and high dose group (7.5,15,30 mg · kg-1) in the modeling, intraperitoneal evenly with a syringe applied to the wound, and the amount of 10 d amplification, one-time administration . The rats in each group were sacrificed on the 11th day after operation. The contents of IL-6, IL-18 and TNF-α in the peritoneal fluid were measured by ELISA. The activities of superoxide dismutase (SOD), nitric oxide synthase (NOS), reduced glutathione (GSH), catalase (CAT) and glutathione peroxidase Malondialdehyde (MDA), nitric oxide (NO) content, meanwhile, the level of intestinal adhesion was recorded. Obtain adhesion intestinal tissue to observe the pathological changes. Results: Compared with the normal group, the levels of IL-6, IL-18 and TNF-α in peritoneal fluid increased (P <0.01) and the activities of MDA, NO and NOS increased , GSH, SOD activity decreased (P <0.01). Compared with the model group, the intestinal adhesion of Ligustrazine microemulsion gel in low, middle and high dose groups was significantly reduced (P <0.05, P <0.01), the pathological changes of intestinal adhesion were gradually released, IL-6 and IL (P <0.05, P <0.01). The content of MDA and NO and the activity of NOS in the adhesion tissue were significantly decreased (P <0.05, P <0.01), and the activities of CAT, GPx, GSH and SOD Enhanced (P <0.05, P <0.01). Conclusion: Ligustrazine microemulsion gel can significantly reduce the degree of intestinal adhesion, intestinal adhesion has a preventive effect. Its role may be down-regulation of IL-18 expression, thereby reducing the expression of related genes, leading to downstream inflammatory cytokines such as TNF-α, IL-6 expression decreased, while anti-intestinal tissue injury related to peroxidation.