摘要
当今脑血管疾病在世界范围内仍为第三大死因,因此这方面的研究一直是目前医学研究热点之一。脑卒中一旦发生,严重影响患者生存质量,甚至危及生命。虽然脑卒中的治疗措施很多,如中医、西医等方法,但其疗效都不尽人意。因此,脑卒中重在预防,贵在预防。近几年来,在脑保护研究领域兴起的药物预处理方法实质上是一种预防措施。一些麻醉药预处理的脑保护作用已被研究证实。地氟醚预处理是否诱导脑缺血耐受作用的产生及其机制等方面的研究尚未见报道。本实验采用大鼠局灶性脑缺血模型,首次应用DWI磁共振技术评估缺血再灌注24h脑梗死容积,旨在探讨:(1)重复地氟醚预处理是否诱导产生延迟性脑缺血耐受作用;(2)单次短时间地氟醚预处理诱导急性脑缺血耐受的可行性;(3)腺苷A_1受体拮抗剂对地氟醚预处理诱导急性脑缺血耐受的影响。
实验一:目的 探讨地氟醚预处理对脑局灶性缺血损伤的影响。方法采用大脑中动脉阻闭(middle cerebral artery occlusion,MCAO)模型,将30只雄性SD大鼠随机分成3组:对照组(C组,n=10),动物不接受任何处理;地氟醚组(Des组,n=10),动物每天接受1h的地氟醚预处理(5.7%地氟醚,94%O_2),连续5 d:吸O_2组(O_2组,n=10),动物每天接受吸
第四军巴大学硕士学位论文
94%O。lh行预处理,连续 5 d。所有动物均在大脑中动脉阻闭 120 in后
恢复再灌注,观察再灌注后24 h动物神经行为学改变及脑梗死容积。结
果 再灌注后 24 h神经行为学评分 D:S组明显低于 C组和 O。组仔<0刀 1):
24 h脑梗死容积C组为2761 士155 石3 mm3刀。组为253.84土门.39…3,
Des组 59.56130.37。’,Des组明显低于对照组(P<0.of)。结论重复地
氟醚预处理可诱导延迟性脑缺血耐受,对大鼠局灶性脑缺血损伤产生保护
作用。
实验二:目的探讨单次短时间地氟醚预处理诱导急性脑缺血耐受的
可行性。摊30只雄性SD大鼠口80~3209),随机分为三组:对照组a
grOOp,fi习 只),动物不接受任何处理:吸氧气组*北roup,p习 只),动
物接受lh吸氧预处理四4%氧气);地氟醚组①es gToup,n习 只),动物接
受lh的地氟醚预处理*.7%地氟醚)。所有动物均采用右侧颈动脉丝线栓
塞大脑中动脉致局灶性脑缺血 120min,观察再灌注后 24h动物神经行为
学改变及脑梗死容积(TTC染色法和核磁共振检测)。结果直肠温度、PH。
PaO。、PaCO。、血压及血糖在预处理期间三组无明显差异。再灌注后 24 h
神经行为学评分地氟醚组明显低于吸氧组和对照组仔奶刀5);地氟醚组
24h脑梗死容积(TI’C:323.44土50.12…’;DWI:281.48土35.16**3)明显
低于吸氧组(hC:427.96上87.26**’;DWI:386.70t27*6**’)和对只
组(h C:498土43.88一’;D WWL 402.53t28.14 nil’),后两组梗死容积
无显著性差异(P>0刀5)。结论单次短时间地氟醚预处理可通过诱导急性脑
缺血耐受而产生脑保护作用。
实验三 目的 探讨腺昔AI受体桔抗剂对地氟醚短时预处理诱导急性
脑缺血耐受的影响。摊:36只雄性SD大鼠椭0~3209),随机分为6
组(+=6):生理盐水+地氟醚组(S ALALmE+D+S组),二甲亚矾+地氟醚组
(DMSO+DCS组),腺昔AI受体桔抗剂+地氟醚组(DPCPX+DCS组),生
理盐水+氧气组(SALINE+OZ组),二甲亚矾+氧气组(DMSO+OZ组),腺
2
第囚军巴大学田士学位沦文
昔 AI受体桔抗剂+氧气组(DPCPX+OZ组)。地氟醚预处理*刀 MAC,60drifl)
或吸氧预处理前30ban分别经腹腔注射生理盐水2.snl.-Mrag,DMSO
2.Sill.-rareg和DPCPX lm叭g。预处理结束*后,所有动物均采用右侧颈动
脉丝线栓塞大脑中动脉,致局灶性脑缺血 120drin,观察髓注后 24h动
物神经行为学改变及脑梗死容积懈量方法同实验二卜结果直肠温度
PaO。、PaCO。、血压及血糖在预处理期间三组间无明显差异。再灌后24h
神经行为学评分及脑梗死容积DPCPX+Des组明显高于SALWE+Des组和
**SO十*es组,与吸氧预处理各组元明显差异:吸氧预处理3组间也无
显著性差异。结论腺昔山受体阻滞剂DPCPX可消除短时地氟醚预处理
诱导的急性脑缺血耐受作用。
Nowdays cerebrovascular diseases still are the third cause for death in the whole world, therefore the study in this field has been an important aspect of medical research. Once stroke occurs, it often leads to neurologic deficit which seriously influence the quality of life and even threaten the life of patients. Although many protective treatment measures, such as Chinese medical science and western medicine, against brain ischemia damage have been found, few of them show satisfactory curative effect. Therefore, prevention measures are gradually emphasized in the treatment of brain ischemia. Recently, a lot of studies have focused on preconditioning measures of brain ischemia . Some anesthetics have been proved to have preconditioning effect on brain ischemia. However, whether desflurane preconditioning can induce brain ischemic tolerance has not been reported. In this study, we evaluated the effects of desflurane preconditioning of neuroprotection against middle cerebral artery occlusion injury in rat with diffusion -weighted MR imaging for the first time. The present study was designed to evaluate the following objectives in a rat middle cerebral artery occlusion (MCAO) model. (1) To investigate if desflurane preconditioning induces ischemic tolerance
against neuronal injury produced by MCAO in rats.(2) To investigate if once short-duration desflurane preconditioning induces ischemic tolerance against brain injury produced by MCAO in rats.(3) To investigate the effects of DPCPX, an adenosine receptor antagonist, on the brain ischemic tolerance induced by preconditioning with once short-duration desflurane. Experiment 1:
AIM To investigate if desflurane preconditioning induces delayed ischemic tolerance against neuronal damage produced by MCAO in rats. METHODS Thirty male Sprague-Dawley (SD) rats weighing 280-320g were randomly divided into three groups: control group (C), without pretreatment; desflurane preconditioning group (Des), inhalation of 5.7% desflurane mixing with 94% O2 lh per day for 5d;oxygen preconditioning group (Oi), inhalation of 94%O2 1h per day for 5d. Right MCAO (120min) was induced by a 3-0 nylon thread with round tip inserted cranially into right internal carotid artery. The neurologic deficit score (NDS) was evaluated 24h after reperfusion and the infarct volume was determined 24h after reperfusion. RESULTS The NDS of Des group was lower than other two groups (P<0.01). The infarct volume of C, O2 and Des group was (276.10+155.63) mm3, (253.84+174.39) mm3 and (59.56+30.37) mm3 respectively. The difference between Des group and C group was significant (P<0.01). CONCLUSION Desflurane pretreatment was able to induce delayed ischemic tolerance against neuronal injury produced by transient MCAO in rats. Experiment 2:
AIM To investigate if once short-duration desflurane preconditioning induces acute ischemic tolerance against brain injury produced by MCAO in rats. Methods Thirty male SD rats weighing 280-320 g were randomized into three
groups: control group (C), without pretreatment; oxygen-inhaling group (O2), with inhaling 94% O2 1h; desflurane preconditioning group, inhalation of 5.7% desflurane mixing with 94% O2 1h, n=10, (Des). Each animal was then subjected to 2-hour MCAO by the intraluminal suture technique. The NDS were evaluated 24h after reperfusion and the infarct volume were measured with diffusion-weighted imaging (DWI) and TTC staining at 24 hours of reperfusion. Results Rectal temperature, PH, PaO2, PaCO2, blood pressure and blood glucose were controlled and not different among groups during preconditioning. The NDS of Des group was lower than those of other two groups at 24 hours of reperfusion. The infarct volume was smaller in Des group(TTC:323.44+50.12 mm3 ;DWI:281.48+35.16mm3) compared with O2 group (TTC:427.96+87.26 mm3 ;DWI:386.70+27.86 mm3) and control group (TTC:498+43.88 mm3;DWI: 402.53+28.14 mm3), but the infarct volume was no significant difference between O2 group and control group (P>0.05). Conclusions Once short-duration desflurane pretrea
引文
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