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目的评估促红细胞生成素(EPO)及其衍生肽(HBSP)在尿源性脓毒血症致兔急性肾损伤及炎症反应中的保护作用。方法将24只新西兰大白兔随机均分为US组[将800μg/kg内毒素(LPS)1mL注入左侧输尿管内,在注射点上方结扎输尿管,逐层缝合关闭腹腔]、Sham组(不结扎输尿管和注射LPS,其余操作同US组)、EPO治疗组(建模后经耳缘静脉给予EPO 5000IU/kg体质量)、HBSP治疗组(建模后经耳缘静脉给予HBSP60μg/kg体质量,每6小时1次)。采用肾盂高压法建立上尿路急性梗阻并脓毒血症新西兰大白兔模型。于术前及术后12、24、36h采血检测血肌酐(Cr)、尿素氮(BUN)、谷丙转氨酶(ALT)、谷草转氨酶(AST),酶联免疫吸附测定(ELISA)法检测血清中肿瘤坏死因子(TNF)-a、白细胞介素(IL)-6。术后36h行HE染色光学显微镜下观察肾脏、肝脏、肺脏组织病理学变化。US组结果与Sham组比较,确定尿源性脓毒血症兔模型是否建立。EPO治疗组、HBSP治疗组结果与US组比较,评估EPO和HBSP在尿源性脓毒血症致兔急性肾损伤及炎症发应中的保护作用。结果与Sham组相比,术后12、24、36h,US组Cr、BUN、ALT、AST、TNF-a、IL-6均明显升高,差异有统计学意义(P<0.01),与US组相比,EPO治疗组及HBSP治疗组各时间点Cr、BUN、ALT、AST、TNF-a、IL-6水平无明显下降,差异无统计学意义(P>0.05)。光镜下观察组织病理学改变,与US组相比,EPO治疗组及HBSP治疗组肾脏、肝脏及肺脏组织损伤评分差异无统计学意义(P>0.05)。结论促红细胞生成素及其衍生肽对尿源性脓毒血症兔急性肾损伤无明显保护作用,对炎症反应亦无明显抑制作用。
Objective To evaluate the protective effect of erythropoietin (EPO) and its derived peptide (HBSP) on acute kidney injury and inflammation induced by urinary sepsis in rabbits. Methods Twenty-four New Zealand white rabbits were randomly divided into the US group [1 mL of 800 μg / kg LPS was injected into the left ureter, the ureter was ligated above the injection site, and the abdominal cavity was closed one by one) Sham group And EPO group (EPO 5000IU / kg body weight after EPR treatment), HBSP treatment group (body weight of 60μg / kg HBSP was given via ear vein after modeling, 6 hours once). Establishment of a New Zealand White Rabbit Model of Upper Ureocular Obstruction and Sepsis by Pyelography. The levels of serum creatinine (Cr), blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and enzyme linked immunosorbent assay (ELISA) were measured before and 12, 24, Tumor necrosis factor (TNF) -a, interleukin (IL) -6. The histopathological changes of kidney, liver and lung were observed under light microscope at 36 hours after operation. The results of the US group were compared with the Sham group to determine if the urine-derived sepsis rabbit model was established. The results of EPO treatment group and HBSP treatment group were compared with those of the US group to evaluate the protective effect of EPO and HBSP in acute renal injury and inflammation induced by urinary sepsis in rabbits. Results Compared with Sham group, the levels of Cr, BUN, ALT, AST, TNF-α and IL-6 in the US group were significantly increased at 12, 24 and 36 h after operation (P <0.01) There was no significant difference in the levels of Cr, BUN, ALT, AST, TNF-a and IL-6 between EPO treatment group and HBSP treatment group at each time point (P> 0.05). Histopathological changes were observed under light microscope. Compared with the US group, there was no significant difference in the damage scores of the kidney, liver and lung tissue between the EPO treatment group and the HBSP treatment group (P> 0.05). Conclusion Erythropoietin and its derived peptides have no significant protective effect on acute renal injury induced by urinary sepsis in rabbits, and have no obvious inhibitory effect on inflammatory reaction.