中华神经医学杂志
中華神經醫學雜誌
중화신경의학잡지
CHINESE JOURNAL OF NEUROMEDICINE
2009年
12期
1226-1230
,共5页
罗成义%郭燕舞%柯以铨%徐如祥%河井信行%田宫隆
囉成義%郭燕舞%柯以銓%徐如祥%河井信行%田宮隆
라성의%곽연무%가이전%서여상%하정신행%전궁륭
血管紧张素Ⅱ%受体拮抗剂%自发性高血压%脑出血
血管緊張素Ⅱ%受體拮抗劑%自髮性高血壓%腦齣血
혈관긴장소Ⅱ%수체길항제%자발성고혈압%뇌출혈
Angiotensin Ⅱ%Receptor blocker%Spontaneously hypertension%Intracerebral hemorrhage
目的 研究血管紧张素Ⅱ-1型受体拈抗剂奥美沙坦(OLM)在自发性高血压大鼠脑出血中的神经保护作用. 方法 自发性高血压大鼠采用完全随机数字表法分成正常组、脑出血组、治疗对照组、OLM治疗组,每组11只.正常组不做任何处理,后3组经右侧基底节注射胶原蛋白酶Ⅶ制作实验性脑出血模型.脑出血后1 h,OLM组经胃管给予单剂量鼻饲OLM(10 mg/kg或3mg/kg,溶入1 mL羧甲基纤维素钠中),治疗对照组给予等量羧甲基纤维素钠,脑出血组不予处理.脑出血后6h,在动物清醒状态下,用无创鼠尾血压计测平均动脉血压;脑出血后24 h,按改良型肢体平衡试验法进行行为学检测,干湿法测脑组织含水量,RT-PCR分析受体和靶基因mRNA表达水平. 结果 脑出血组平均动脉血压[(121.4+3.5)mm Hg]与正常组基础血压[(120.2+3.8)mm Hg]比较差异无统计学意义(P>0.05);10 mg/kg OLM组平均动脉血压[(105.6+3.5)mm Hg]较脑出血组明显下降,差异有统计学意义(P<0.05);但3 mg/kg OLM组和治疗对照组没有引起血压的明显下降[分别为(120.8±3.1)mm Hg,(118.6±3.9)mm Hg],与脑出血组比较差异无统计学意义(P>0.05).3 mg/kgOLM组大鼠出血侧脑组织含水量[(80.02±0.32)%]较脑出血组[(80.90±0.36)%]减少,差异有统计学意义(P<0.05);治疗对照组大鼠出血侧脑组织含水量[(80.81±0.32)%]较脑出血组稍低,但差异无统计学意义(P>0.05).3 mg/kg OLM组表现出更少的神经功能缺失(神经功能评分为5.03±0.71),与脑出血组(6.62±0.55)比较差异有统计学意义(P<0.05);治疗对照组神经功能评分(6.41±0.55)与脑出血组比较差异无统计学意义(P>0.05).3 mg/kg OLM组脑出血侧ATIR及靶基因(HO-1、COX-2、IL-6和VCAM-1)的mRNA表达均比脑出血组低,差异有统计学意义(P<0.05),而治疗对照组和脑出血组比较差异无统计学意义(P>0.05). 结论 在白发性高血压大鼠脑出血中,小剂量OLM能促进神经功能的恢复并产生许多神经保护作用,包括减轻脑水肿、抑制炎症反应和氧化应激反应等.
目的 研究血管緊張素Ⅱ-1型受體拈抗劑奧美沙坦(OLM)在自髮性高血壓大鼠腦齣血中的神經保護作用. 方法 自髮性高血壓大鼠採用完全隨機數字錶法分成正常組、腦齣血組、治療對照組、OLM治療組,每組11隻.正常組不做任何處理,後3組經右側基底節註射膠原蛋白酶Ⅶ製作實驗性腦齣血模型.腦齣血後1 h,OLM組經胃管給予單劑量鼻飼OLM(10 mg/kg或3mg/kg,溶入1 mL羧甲基纖維素鈉中),治療對照組給予等量羧甲基纖維素鈉,腦齣血組不予處理.腦齣血後6h,在動物清醒狀態下,用無創鼠尾血壓計測平均動脈血壓;腦齣血後24 h,按改良型肢體平衡試驗法進行行為學檢測,榦濕法測腦組織含水量,RT-PCR分析受體和靶基因mRNA錶達水平. 結果 腦齣血組平均動脈血壓[(121.4+3.5)mm Hg]與正常組基礎血壓[(120.2+3.8)mm Hg]比較差異無統計學意義(P>0.05);10 mg/kg OLM組平均動脈血壓[(105.6+3.5)mm Hg]較腦齣血組明顯下降,差異有統計學意義(P<0.05);但3 mg/kg OLM組和治療對照組沒有引起血壓的明顯下降[分彆為(120.8±3.1)mm Hg,(118.6±3.9)mm Hg],與腦齣血組比較差異無統計學意義(P>0.05).3 mg/kgOLM組大鼠齣血側腦組織含水量[(80.02±0.32)%]較腦齣血組[(80.90±0.36)%]減少,差異有統計學意義(P<0.05);治療對照組大鼠齣血側腦組織含水量[(80.81±0.32)%]較腦齣血組稍低,但差異無統計學意義(P>0.05).3 mg/kg OLM組錶現齣更少的神經功能缺失(神經功能評分為5.03±0.71),與腦齣血組(6.62±0.55)比較差異有統計學意義(P<0.05);治療對照組神經功能評分(6.41±0.55)與腦齣血組比較差異無統計學意義(P>0.05).3 mg/kg OLM組腦齣血側ATIR及靶基因(HO-1、COX-2、IL-6和VCAM-1)的mRNA錶達均比腦齣血組低,差異有統計學意義(P<0.05),而治療對照組和腦齣血組比較差異無統計學意義(P>0.05). 結論 在白髮性高血壓大鼠腦齣血中,小劑量OLM能促進神經功能的恢複併產生許多神經保護作用,包括減輕腦水腫、抑製炎癥反應和氧化應激反應等.
목적 연구혈관긴장소Ⅱ-1형수체념항제오미사탄(OLM)재자발성고혈압대서뇌출혈중적신경보호작용. 방법 자발성고혈압대서채용완전수궤수자표법분성정상조、뇌출혈조、치료대조조、OLM치료조,매조11지.정상조불주임하처리,후3조경우측기저절주사효원단백매Ⅶ제작실험성뇌출혈모형.뇌출혈후1 h,OLM조경위관급여단제량비사OLM(10 mg/kg혹3mg/kg,용입1 mL최갑기섬유소납중),치료대조조급여등량최갑기섬유소납,뇌출혈조불여처리.뇌출혈후6h,재동물청성상태하,용무창서미혈압계측평균동맥혈압;뇌출혈후24 h,안개량형지체평형시험법진행행위학검측,간습법측뇌조직함수량,RT-PCR분석수체화파기인mRNA표체수평. 결과 뇌출혈조평균동맥혈압[(121.4+3.5)mm Hg]여정상조기출혈압[(120.2+3.8)mm Hg]비교차이무통계학의의(P>0.05);10 mg/kg OLM조평균동맥혈압[(105.6+3.5)mm Hg]교뇌출혈조명현하강,차이유통계학의의(P<0.05);단3 mg/kg OLM조화치료대조조몰유인기혈압적명현하강[분별위(120.8±3.1)mm Hg,(118.6±3.9)mm Hg],여뇌출혈조비교차이무통계학의의(P>0.05).3 mg/kgOLM조대서출혈측뇌조직함수량[(80.02±0.32)%]교뇌출혈조[(80.90±0.36)%]감소,차이유통계학의의(P<0.05);치료대조조대서출혈측뇌조직함수량[(80.81±0.32)%]교뇌출혈조초저,단차이무통계학의의(P>0.05).3 mg/kg OLM조표현출경소적신경공능결실(신경공능평분위5.03±0.71),여뇌출혈조(6.62±0.55)비교차이유통계학의의(P<0.05);치료대조조신경공능평분(6.41±0.55)여뇌출혈조비교차이무통계학의의(P>0.05).3 mg/kg OLM조뇌출혈측ATIR급파기인(HO-1、COX-2、IL-6화VCAM-1)적mRNA표체균비뇌출혈조저,차이유통계학의의(P<0.05),이치료대조조화뇌출혈조비교차이무통계학의의(P>0.05). 결론 재백발성고혈압대서뇌출혈중,소제량OLM능촉진신경공능적회복병산생허다신경보호작용,포괄감경뇌수종、억제염증반응화양화응격반응등.
Objective To investigate the neuroprotective effects of angiotensin Ⅱ type 1 receptor (AT1R) blocker olmesartan medoxomil (OLM) on intracerebral hemorrhage (ICH) in spontaneously hypertensive rats (SHRs). Methods SHRs (male, 12 weeks old; weighing 300±20 g) were randomly assigned to normal, ICH, vehicle-treatment ICH (control), OLM-treatment ICH (OLM) groups. ICH was induced via stereotaxic right basal ganglia administration of collagenase type Ⅶ. One hour after ICH, the rats in OLM group were given a single oral dose of OLM (10 or 3 mg/kg solved in 1 mL sodium carboxymethylcellulose) via nasogastric feeding, and those in the control group received an equal volume of sodium carboxymethylcellulose only. Six hours after ICH induction, mean arterial blood pressure (MAP) was measured using the non-invasive method of tail-cuff plethysmography in conscious rats. Twenty-four hours after ICH induction, neurobehavior was detected by the modified limb placing test (MLPT); brain water content was measured by dry-wet method; the mRNA expression levels of receptor and target genes were analyzed by real-time PCR. Results MAP in the ICH group ([121.4±3.5] mm Hg) did not significantly differ from baseline pressure in the normal group ([120.2±3.8] mm Hg)(P>0.05); MAP in the OLM group with 10 mg/kg ([105.6±3.1] mm Hg) was significantly lower than that in the ICH group (P<0.05); the OLM group with 3 mg/kg ([120.8±3.1] mm Hg) and control group ([118.6±3.9] mm Hg) did not induce blood pressure reduction, and did not show significant difference as compared with the ICH group (P>0.05). In the hemorrhagic hemisphere, brain water content in the OLM group with 3 mg/kg (80.02%±0.32%) had significant difference from that in the ICH group (80.90%±0.36%, P< 0.05); brain water content of the control group (80.81%±0.32%) was slightly lower than that of the ICH group, without significant differences (P>0.05). The OLM group with 3 mg/kg (5.03±0.71) was showed significantly lower score of MLPT as compared with that in the ICH group (6.62±0.55, P<0.05). The score of MLPT in the control group (6.41 ±0.55) did not differ from that in the ICH group (P>0.05). In the hemorrhagic hemisphere, the mRNA expressions of AT1R and target genes, such as HO-1, COX-2, IL-6 and VCAM-1, in the OLM group with 3 mg/kg were significantly lower than those in the ICH group (P<0.05), but the difference between the control and ICH groups did not show statistical significance (P>0.05). Conclusion Treatment with low doses of OLM in the experimental ICH of SHRs may promote its neurological recovery and induce its neuroprotective effects, including reduction of edema, inhibition of inflammation and oxidative stress.
