HSP70在感染性休克大鼠肾组织中的表达及氯胺酮的干预作用

发布时间：2018-11-20 16:26

【摘要】：目的本实验旨在观察感染性休克大鼠不同时间点平均动脉压(MAP)、肾组织热休克蛋白70(HSP70)、血肌酐(Cr)、尿素氮(BUN)的变化,以及氯胺酮对它们的影响,探讨感染性休克大鼠肾脏损伤,HSP70的演变及氯胺酮的干预机制。方法选健康雄性Wistar大鼠54只,随机分为三组：假手术(SHAM)组、盲肠结扎加穿孔(CLP)组及氯胺酮(KT)组。各组大鼠术前均行颈总动脉置管术,连续监测并记录平均动脉压。术毕均经尾静脉给予生理盐水持续补液至实验结束,速率为10ml·kg-1·h-1。SHAM组开腹后不做任何处理,其余两组行盲肠结扎穿孔术(CLP)。备皮消毒后,沿腹中线剪开中下腹部皮肤约2cm,游离肠系膜和盲肠,用3-0丝线环行结扎盲肠根部,用9号针头在盲端穿刺2处,两针孔相距约3mm,轻轻挤压盲肠至少量粪渣流出,还纳肠管,并逐层缝合关腹。碘伏消毒并包扎伤口。KT组于CLP前20min腹腔给药40 mg/kg。各组在3h、6h、12h分别经心脏采血,检测尿素氮和肌酐的含量,并用免疫组化方法检测热休克蛋白70(HSP70)的表达。结果①一般情况及大体形态学：与SHAM组比较,CLP组大鼠精神萎靡,嗜睡,活动减少,甚至出现呼吸急促,眼角分泌物等。实验完毕后处死动物,观察腹腔有脓液或血性渗出物渗出,恶臭,盲肠肿胀变黑,坏疽、粘连,肝肾等器官充血水肿,有时表面可见出血点;KT组明显减轻。②血流动力学改变：各组动物术后平均动脉压均呈进行性下降。CLP组和KT组在9h后MAP明显下降(P0.01)；KT组MAP下降较CLP组明显减轻(P＜0.01)。③血清肌酐(Cr)含量的变化：在3h和6h两个时间点没有明显变化；术后12h,与SHAM组比较,CLP组大鼠血清Cr显著升高(P0.01)；KT组血清Cr较CLP组明显降低(P0.05)。④尿素氮含量的变化：与SHAM组比较,CLP组大鼠血清BUN含量在术后6h和12h显著升高(P＜0.01)；与CLP组比较,KT组大鼠血清BUN含量在6、12h时相点明显降低(P0.05)。⑤HSP70表达量的变化：三组肾组织中HSP70均有表达,CLP组及KT组均明显高于SHAM组(P0.01)；KT组明显高于CLP组(P0.05)。结论感染性休克时肾组织中HSP70的含量显著增高,并且随时间的推移而逐渐增强,而氯胺酮能抑制脓毒症大鼠血清BUN和Cr的增高,减轻肾组织损害,对脓毒症大鼠肾脏具有一定的保护,此作用可能与诱导HSP70表达增强有关。
[Abstract]:Objective to observe the changes of heat shock protein 70 (HSP70) and serum creatinine (Cr),) urea nitrogen (BUN) in renal tissue of (MAP), at different time points in rats with septic shock and the effect of ketamine on them. To investigate the renal injury, the evolution of HSP70 and the intervention mechanism of ketamine in septic shock rats. Methods 54 healthy male Wistar rats were randomly divided into three groups: sham operation (SHAM) group, cecal ligation plus perforated (CLP) group and ketamine (KT) group. The common carotid artery catheterization was performed before operation and the mean arterial pressure was continuously monitored and recorded. At the end of the operation, all the patients received continuous infusion of normal saline through the caudal vein until the end of the experiment at the rate of no treatment after laparotomy in the 10ml kg-1 h-1.SHAM group, and (CLP). Was performed in the other two groups with cecal ligation and perforation. After disinfecting the skin, the skin of the middle and lower abdomen was cut along the midabdominal line about 2 cm, the mesentery and caecum were free, the root of the caecum was ligated with 3-0 silk thread, and the two pinholes were about 3 mm apart. Gently squeeze the cecum to a small amount of fecal residue, return the intestinal tube, and close the abdomen layer by layer. Iodophor was disinfected and wound bandaged. KT group received intraperitoneal administration of 20min for 40 mg/kg. before CLP. The blood samples were collected from the heart at 3 h, 6 h and 12 h, respectively. The contents of urea nitrogen and creatinine were measured, and the expression of heat shock protein 70 (HSP70) was detected by immunohistochemical method. Results 1 General condition and general morphology: compared with SHAM group, the rats in CLP group were depressed in spirit, drowsiness, decreased in activity, and even appeared shortness of breath, eye horn secretion and so on. At the end of the experiment, the animals were killed to observe the exudation of pus or blood exudates, stench, swelling and blackening of caecum, gangrene, adhesion, hyperemia and edema of liver and kidney, and some bleeding spots were observed on the surface. The hemodynamic changes in KT group were significantly alleviated. 2 the mean arterial pressure in each group was decreased progressively, while MAP in CLP group and KT group decreased significantly after 9 hours (P0.01). The decrease of MAP in KT group was significantly less than that in CLP group (P < 0. 01). 3 the change of serum creatinine (Cr) was not obvious at 3 h and 6 h, but at 12 h after operation, the serum Cr in CLP group was significantly higher than that in SHAM group (P0.01). The level of serum Cr in KT group was significantly lower than that in CLP group (P0.05). 4 the level of serum BUN in CLP group was significantly higher than that in SHAM group at 6 and 12 hours after operation (P < 0. 01). Compared with CLP group, the content of serum BUN in KT group was significantly decreased at 6h / 12h (P0.05). The change of 5HSP70 expression was found in renal tissue of three groups. The expression of HSP70 in CLP group and KT group was significantly higher than that in SHAM group (P0.01). KT group was significantly higher than CLP group (P0.05). Conclusion during septic shock, the content of HSP70 in renal tissue increases significantly, and gradually increases with time. Ketamine can inhibit the increase of serum BUN and Cr in septic rats and alleviate the damage of renal tissue. It can protect the kidney of sepsis rats, which may be related to the increase of HSP70 expression.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R363

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