己酮可可碱对脓毒症大鼠肠HSP 70、NF-κB和细胞凋亡的影响

Effects of Pentoxifylline on the Expression of HSP 70,NF-κB and Apoptosis in Intestinal Tissues of Rats with Sepsis

目的探讨己酮可可碱(pentoxifylline,PTX)对脓毒症大鼠肠热休克蛋白70(HSP70)、核因子-κB(NF-κB)和细胞凋亡的影响。方法盲肠结扎穿孔(CLP)制备脓毒症大鼠模型,实验动物随机分成3组:假手术组(S)、脓毒症组(CLP)、治疗组(PTX,CLP术后经颈外静脉注射PTX)。ELISA测定血浆TNF-α水平,原位末端缺口标记法(TUNEL)检测肠上皮细胞凋亡,Westernblot法检测肠组织内HSP70和NF-κB蛋白表达,黄嘌呤氧化酶法测肠组织内SOD活性。结果脓毒症时,血浆TNF-α、肠上皮细胞凋亡和肠组织内HSP70、NF-κB水平明显增加,而肠组织内SOD活性降低(均P<0.01)。经过PTX处理后,肠组织内HSP70水平进一步增加(P<0.01),血浆TNF-α、肠上皮细胞凋亡和肠组织内NF-κB水平明显降低,肠组织内SOD活性增加(均P<0.01)。结论 PTX可以通过增加肠组织内HSP70水平,发挥其内源性保护作用,进而抑制NF-κB,减轻肠上皮细胞凋亡,保护肠组织。

Objective To study the effects of pentoxifylline（PTX）on the expression of HSP 70,NF-κB and apoptosis in intestinal tissues of rats with sepsis.Methods Rat sepsis model was established by using cecal ligation and puncture（CLP）.Twenty-four Wistar rats were randomly divided into 3 groups：sham operated control group（S）,sepsis group（CLP）,and PTX treatment group（PTX）.ELISA was used to assess the level of TNF-α.TUNEL was used to assay apoptosis.Western blot was used to detect the expression of HSP 70 and NF-κB in intestinal tissues.The levels of SOD were determined.Results The levels of TNF-α,apoptosis index,HSP 70 and NF-κB in CLP group were higher than those in S group（P〈0.01）,but the level of SOD in CLP group was lower than in S group（P〈0.01）.After PTX treatment,the levels of HSP 70 in the myocardial tissues in PTX group were higher than those in CLP group（P〈0.01）,but the levels of TNF-α,apoptosis index and NF-κB in PTX group were lower than those in CLP group（P〈0.01）,the level of SOD in PTX group was higher than that in CLP group（P〈0.01）.Conclusion PTX can protect the intestinal tissues by elevating the expression of HSP 70 and reducing the expression of NF-κB and apoptosis index.