瓜氨酸对盲肠结扎穿孔脓毒症大鼠模型急性肾损伤的保护作用研究

Protective effects of citrulline on acute kidney injury induced by sepsis

目的探讨瓜氨酸对盲肠结扎穿孔脓毒症大鼠模型急性肾损伤的保护作用。方法选取96只成年雄性Wistar大鼠,按随机数字表法分为对照组、假手术组、脓毒症组、治疗组,每组6只。对照组不经任何处理;假手术组仅开腹翻动肠管后关腹;脓毒症组与治疗组行盲肠结扎穿孔术(Cecal Ligation and Puncture,CLP));治疗组术前一周胃饲L-瓜氨酸200mg/kg·d-1。造模24h取血、处死大鼠,测定各组血清尿素氮(BUN)和肌酐(Cr)浓度;肾脏组织行苏木素-伊红(HE)染色观测组织病理学改变;运用悬浮液相芯片技术检测各组肾脏组织中肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)的表达水平。结果与假手术组相比,脓毒症组血清尿毒氮、肌酐及肾组织TNF-α、IL-6水平均显著升高(P<0.05),肾组织HE染色显示大量炎性细胞浸润,肾小管上皮细胞肿胀、空泡变性。与脓毒症组相比,治疗组血清尿毒氮、肌酐及肾组织TNF-α、IL-6水平均明显下降,但仍高于假手术组(P<0.05)。肾组织病理改变也明显减轻。结论瓜氨酸可抑制肾脏组织中促炎细胞因子TNF-α、IL-6的表达,说明瓜氨酸可能通过调节细胞因子表达水平,从而在脓毒症肾损伤的发生发展过程发挥保护作用。

Objective To investigate the protective effects on acute renal injury in rats with sepsis.Methods 96 cases of healthy and male Wistar rats were randomly divided into 4groups which were control group（n=6）,sham operation group（n=6）,sepsis group（n=6）and treatment group（n=6）.Normal control group without any Processing.Animal in sham group did laparotomy flip cecum after anesthesia,then closed the Peritoneal.Sepsis model was reproduced in sepsis group and treatment group with cecal ligation and puncture（CLP）,and the rats of treatment group were given L-citrulline 200 mg kg^-1·d^-1 for 7days before operation.The rats were killed at 24 hafter operation.Then the concentrations of serum BUN and Cr,the histopathological changes of kidney were merasured,simultaneously monitored the expression level of TNF-α and IL-6in kidney tissue by liquid chip technology.Results The Serum BUN,Cr and TNF-α,IL-6level in the sepsis group were significantly increased more than those in the sham operation group（P〈0.05）.Compared with the sepsis group,The Serum BUN,Cr and TNF-α,IL-6level in the treatment group were significantly decreased（P〈0.05）.Conclusion citrulline inhibit the expression of proinflammatory cytokines TNF-α,IL-6in renal tissue and reduce serum BUN and Cr concentration,improve kidney function and reduce renal histopathological damage in rats with sepsis.Description citrulline may pass regulate cytokines expression level,which is a protection role in the process of the development of sepsis-induced renal injury.