右美托咪定联合舒芬太尼对高血压性脑出血大鼠脑组织形态学改变的研究

Study of Dexmedetomidine Combined Sufentanil on Cerebral Histomorphological Changes in Rats with Hypertensive Cerebral Hemorrhage

目的探究右美托咪定、舒芬太尼及其联合应用对高血压性脑出血大鼠脑组织形态学改变的影响。方法SD大鼠采用随机数字表法分为假手术组、模型组、右美托咪定组、舒芬太尼组、右美托咪定联合舒芬太尼组,制备双肾双夹大鼠肾血管性高血压模型,除假手术组均经右侧尾状核注入含0.4 UⅦ型胶原酶等量生理盐水诱导脑出血,右美托咪定组构建模型前给予5μg/kg盐酸右美托咪定腹腔注射,舒芬太尼组构建模型前给予10μg/kg舒芬太尼腹腔注射,右美托咪定联合舒芬太尼组构建模型前给予5μg/kg盐酸右美托咪定+10μg/kg舒芬太尼腹腔注射。比较各组大鼠术后24 h神经功能缺损程度量表(neurological deficit score,NDS)评分差异、脑组织含水量;采用光学显微镜及电子显微镜观察各组右侧大脑皮层组织形态改变;荧光显微镜观察各组脑组织出血区存活神经元;采用定量试剂盒检测一氧化氮(nitric oxide,NO)含量及一氧化氮合酶(nitric oxide synthase,NOS)活性。结果与假手术组比较,模型组、右美托咪定组、舒芬太尼组、右美托咪定联合舒芬太尼组NDS评分、脑组织含水量、NO含量和NOS活性均明显较高(P均<0.05),存活神经元数量则明显较少(P均<0.05);与模型组比较,右美托咪定组、舒芬太尼组、右美托咪定联合舒芬太尼组大鼠NDS评分、脑组织含水量、NO含量和NOS活性则明显较低(P均<0.05),存活神经元数量则明显较高(P均<0.05);与右美托咪定联合舒芬太尼组比较,右美托咪定组及舒芬太尼组NDS评分、脑组织含水量、NO含量和NOS活性明显较高(P均<0.05),存活神经元数量则明显较少(P均<0.05)。结论右美托咪定联合舒芬太尼能通过增强机体抗氧化能力,影响细胞凋亡,从而有效减轻高血压性脑出血细胞水肿和线粒体肿胀,减轻神经细胞损伤,改善大鼠脑组织水肿状态和NDS评分。

Objective To investigate the effects of dexmedetomidine,sufentanil and their combined application on cerebral histomorphological changes in hypertensive cerebral hemorrhage rats.Methods SD rats were divided into sham operation group,model group,dexmedetomidine group,sufentanil group and dexmedetomidine combined sufentanil group by random number table.The rat model of nephrovascular hypertension with double kidney and double clip was prepared and made,and rats in all groups except sham operation group were injected with normal saline containing 0.4 UⅦcollagenase through the right caudate nucleus to induce cerebral hemorrhage.Dexmedetomidine group was intraperitoneally injected with dexmedetomidine hydrochloride 5μg/kg before model construction;sufentanil group was intraperitoneally injected sufentanil 10μg/kg before model construction;the dexmedetomidine combined sufentanil group was given 5μg/kg dexmedetomidine hydrochloride+10μg/kg sufentanil intraperitoneal injection before model construction.The difference of neurological deficit score(NDS)and water content of brain tissue in each group were compared 24 hours after surgery.The morphological changes of the right cerebral cortex were observed by optical microscope and electron microscope;the surviving neurons in the bleeding area of each group were observed by fluorescence microscope;nitric oxide(NO)content and nitric oxide synthase(NOS)activity were detected by quantitative kit.Results Compared with sham operation group,NDS,brain water content,NO content and NOS activity in model group,dexmedetomidine group,sufentanil group and dexmedetomidine combined sufentanil group were significantly higher(all P<0.05),while the number of surviving neurons was significantly less(all P<0.05);compared with model group,dexmedetomidine group,sufentanil group and dexmedetomidine combined sufentanil group had significantly lower NDS,brain water content,NO content and NOS activity(all P<0.05),while the number of surviving neurons was significantly more(all P<0.05);compared with dexmedetomidine combined sufentanil group,NDS score,brain water content,NO content and NOS activity were significantly higher in dexmedetomidine group and sufentanil group(all P<0.05),while the number of surviving neurons was significantly less(all P<0.05).Conclusion Dexmedetomidine combined sufentanil can effectively reduce cell edema and mitochondrial swelling in hypertensive cerebral hemorrhage by enhancing the antioxidant capacity of the body and affecting cell apoptosis,thus alleviating nerve cell damage and improving cerebral edema and NDS score in rats.