促红细胞生成素对脓毒症大鼠肠道保护作用及机制

PROTECTIVE EFFECT AND MECHANISM OF ERYTHROPOIETIN ON INTESTINAL FUNCTION IN SEPTIC RATS

目的探讨促红细胞生成素（EPO）对脓毒症模型大鼠肠道损伤的保护作用及可能的机制。方法将36只成年雄性清洁级SD大鼠随机分为假手术组、脓毒症组、EPO干预组,每组12只大鼠。采用盲肠结扎穿孔（CLP）法建立脓毒症大鼠模型,建模后EPO干预组立即腹腔注射EPO 3 000U/kg,其他组腹腔注射相同容量的生理盐水,24h后留取各组血清及肠道组织标本,分别检测血清中肿瘤坏死因子-α（TNF-α）、二胺氧化酶（DAO）表达变化,测定肠道组织匀浆中髓过氧化物酶（MPO）、丙二醛（MDA）、EPO受体（EPOR）的含量,免疫组织化学法观察肠道组织核因子κb（NF-κb）表达,并进行苏木精-伊红染色观察肠道组织病理变化。结果 EPO可显著降低脓毒症大鼠血清TNF-α、DAO水平及肠道组织MPO、MDA、NF-κb水平,上调肠道EPOR表达,差异有统计学意义（F=34.96~115.28,q=4.29~12.86,P〈0.01）。EPO可保护肠道结构。结论 EPO对脓毒症模型大鼠肠道的损伤有一定保护作用,主要表现在保护肠道屏障功能、抑制组织氧化及炎症细胞激活,其机制可能与促进EPOR升高、抑制NF-κb通路有关。

Objective To investigate the protective effect of erythropoietin （EPO） on intestinal injury in rats caused by sepsis and its potential mechanism. Methods Thirty-six male adult rats were evenly randomized to three groups as sham-operation group, sepsis group and EPO-treated group. Employing cecal ligation and puncture （CLP） method, a sepsis model in rats was created. Upon completion of the models, the rats in the EPO-treated group were given intra-peritoneal injection of EPO （3 000 U/ kg）, and those in the other two groups were offered same volume of normal saline instead EPO. After 24 h, serum and intestinal tissue samples were collected from each group. The expressions of serum tumor necrosis factor alpha （TNF-α） and diamine oxidase （DAO） were detected, the contents of myeloperoxidase （MPO）, malondialdehyde （MDA） and EPO receptor （EPOR） in intestinal tissue bomogenate measured. Using immunohistotogy, the expression of nuclear factor kappa B （NF-κh） was Observed and HE stained to investigate the pathology changes in intestinal tissue. Results EPO could markedly lower levels of TNF a and DAO in serum, and MPO, MDA, and NF-κb in intestinal tissue, up-regulate the expression of EPOR （F = 34.96- 115.28, q = 4.29 12.86,P〈0.01）, and protect the intestinal structure. Conclusion Erythropoietin has a protective effect on intestine in septic rats, mainly manifests in protecting intestinal barrier function, inhibiting tissue oxidation and the activation of inflammatory cells, the mechanism is likely to be associated with raising the levels of erythropoietin receptor and restraining the NF-κb channel,