活血化瘀法对脓毒症大鼠肾保护作用的实验研究

【作者】 朱雪琦；

【导师】 刘清泉；

【作者基本信息】 北京中医药大学 ， 中西医结合内科， 2005， 硕士

【摘要】 据统计,脓毒症(sepsis)在并发急性肾功能衰竭(ARF)的情况下,病死率可高达 70%。如何早期干预脓毒症 ARF,保护肾功能,防止其形成不可逆的病理损害,关系着脓毒症治疗的全局,是临床面临的严峻问题。中医药作为防治脓毒症不可或缺的干预手段,在防治脓毒症 ARF 方面的报道较少。本研究拟采用与临床脓毒症相关性较强的大鼠盲肠结扎穿孔(CLP)致严重腹腔感染模型,以具有活血化瘀作用的中药作为干预药物,初步探讨活血化瘀法对脓毒症大鼠的肾保护作用,为临床防治脓毒症 ARF 提供新的思路。论文主要包括文献综述和实验研究两部分。文献综述共两篇。第一篇概述了脓毒症动物模型研究进展。动物模型是脓毒症发病机制和临床防治研究的基础。在过去的几十年中,脓毒症发病机制的研究已经取得了长足的进展,但防治方面的研究成果却不尽如人意,许多在临床前动物实验中体现出很好疗效的药物,在临床实验中并未取得预期的结果,值得反思。本文介绍了目前常用的脓毒症动物模型,着重在临床相关性方面进行了评价,为实验研究中动物模型的选择提供一定的参考依据。第二篇概述中医药防治防治急性肾功能衰竭的研究进展,包括辨证论治和方药研究两方面,为本课题活血化瘀的立法原则的提出提供一定的参考。实验研究部分,选用与临床脓毒症相关性较强的大鼠 CLP 模型,以具有活血化瘀作用血的必净注射液作为干预药物,初步探讨活血化瘀法对脓毒症大鼠的肾保护作用。结果显示,CLP 术后,大鼠并发急性肾功能障碍,肾、肝、肺组织发生进行性加重的病理损伤,血清及肾组织中白细胞介素 6(IL-6)的蛋白水平显著升高;血必净注射液可显著延长脓毒症大鼠的生存时间,保护肾功能,减轻组织病理损伤,阻止损伤范围扩大,并可在多时间点显著降低血清及肾组织中IL-6 的水平。结合本实验结果以及相关研究背景知识分析认为,以活血化瘀为立法的血必净注射液对脓毒症大鼠具有肾保护作用,其作用机制可能与调节血清及肾组织中的 IL-6 水平有关。同时提示,以活血化瘀为法防治脓毒症急性肾功能衰竭的思路具有可行性。更多还原

【Abstract】 The combination of sepsis and acute renal failure is associated with 70 percent mortality. It is so important to intervent ARF at its early stage that it is correlate with the overall situation of sepsis intervention. Traditional Chinese medicine is necessary intervention method to prevent and treat sepsis, but there is rarely documented traditional Chinese medicine intervention of acute renal failure in sepsis. Our study will observe the effect of huo xue hua yu method which probably can prevent against renal injury in sepsis using a model of cecal ligation puncture (CLP) in rats, hoping to support a novel idea to prevention and cure ARF associated with sepsis. The thesis mainly includes literature review and laboratory research. The literature reviews consist of two parts. The first one summarizes the development of animal models for sepsis. Over the last decades, there has been great progression on the study of pathogenesis of sepsis. However, it is of interest that so many agents found to be effective in animal models of sepsis have either been ineffective in or have never reached, the stage of clinical trials. In this article the clinically relevance of commonly used models for sepsis are discussed. The second one summarizes the development of prevention and cure of ARF by traditional Chinese medicine. In the experimental study, I investigate the role of Xuebijing in preventing against renal injury using CLP model in rats. After surgery, markers of renal dysfunction increase and histologic examination of HE-stained sections revealed renal, lung and liver time-dependent deteriorating of tissue damage. More extensive tissue damage was seen at 48 hours after CLP. The level of IL-6 increased in serum and renal tissue. Early administration of Xuebijing increased the survival time of rats after CLP, protected renal function, reduced the renal tissue damage, prevent against the more extent tubular injury, and decreased the level of IL-6 which significantly increased after CLP. In conclusion, Xuebijing may protect renal injury of rats after CLP, in part via its inhibition of IL-6. The method of huo xue hua yu may hold promise in clinical settings.更多还原