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目的探讨己酮可可碱对脓毒症大鼠肝组织生物蝶呤产生的影响及其意义。方法采用大鼠盲肠结扎穿孔(CLP)致脓毒症模型,动物随机分为正常对照组、脓毒症组和己酮可可碱治疗组。分别于 CLP 后2,8,16 h 处死动物,检测肝组织生物蝶呤及其合成限速酶—三磷酸鸟苷环水解酶Ⅰ(GTP-CH Ⅰ)mRNA 及肿瘤坏死因子-α(TNF-α)mRNA 表达的改变,同时监测血清肝功能酶学指标的变化。结果脓毒症动物肝组织生物蝶呤含量显著升高,GTP-CH Ⅰ基因表达水平也显著增强,且其改变与局部 TNF-α mRNA 表达水平呈正相关。给予己酮可可碱治疗后2 h,肝组织生物蝶呤含量、GTP-CH Ⅰ及 TNF-α mRNA 表达水平均明显下降(P<0.05),且血清谷丙转氨酶、谷草转氨酶含量也显著降低(P<0.05)。结论脓毒症早期应用己酮可可碱能有效抑制肝组织生物蝶呤及其合成限速酶基因表达,并且明显减轻脓毒症动物肝损害。
Objective To investigate the effects of pentoxifylline on the biopterin production in liver of septic rats and its significance. Methods The model of sepsis induced by cecal ligation and puncture in rats was established. The animals were randomly divided into normal control group, sepsis group and pentoxifylline treatment group. Animals were sacrificed at 2, 8 and 16 hours after CLP, respectively. Biopterin and its synthetic rate-limiting enzyme-GTP-CH Ⅰ mRNA and tumor necrosis factor-α (TNF- α) mRNA expression changes, while monitoring serum liver enzymes changes in the index. Results The liver biopurine content of septic rats was significantly increased, and the expression of GTP-CH Ⅰ gene was also significantly increased. The change was positively correlated with the level of local TNF-α mRNA. After 2 hours of pentoxifylline treatment, the biopterin content, the expression of GTP-CH Ⅰ and TNF-α mRNA in hepatic tissue were significantly decreased (P <0.05), and the contents of alanine aminotransferase and aspartate aminotransferase were also significantly decreased P <0.05). Conclusion Pentoxifylline can effectively inhibit the expression of biopterin and its rate-limiting enzyme in hepatic tissue and significantly reduce hepatic damage in sepsis animals.