异氟醚%认知%受体,高级糖基化终产物%海马
異氟醚%認知%受體,高級糖基化終產物%海馬
이불미%인지%수체,고급당기화종산물%해마
Isoflurance%Cognition%Receptors%Advanced glycation end products%Hippocampus
目的 观察异氟醚对大鼠海马高级糖基化终末产物受体(receptor for advanced glycation end products,RAGE)表达及认知功能的影响.方法 SD雄性老年大鼠(24月龄)45只,SD雄性成年大鼠(4月龄)45只,随机数字表法分为6组(n=15),老年对照组(C1组),成年对照组(C2组):吸入30%氧气的空氧混合气体对照;老年异氟醚单次吸入组(S1组),成年异氟醚单次吸入组(S2组):1.5%异氟醚单次吸入2h;老年异氟醚多次吸入组(R1组),成年异氟醚多次吸入组(R2组):1.5%异氟醚吸入3次,1次/d,2h/次.各组大鼠吸入处理后1d取8只行Morris水迷宫进行认知功能测试,其余大鼠处死取海马,RT-PCR方法测定RAGE mRNA水平,免疫组织化学方法测定RAGE蛋白表达.结果 各组大鼠吸入处理过程中生命体征平稳,血氧饱和度及心率均在正常范围.C1组穿越平台次数为(7.30±2.40)次,探索时间为(49.90±6.22)s,S1、R1组与C1组相比穿越平台的次数减少[穿越平台次数分别为S1(3.90±2.42),R1(3.44±2.40),F=7.448,P<0.01],探索时间缩短[探索时间分别为S1(43.33±7.08)s,R1(39.09±4.56)s,F=7.63,P<0.05],而逃避潜伏期延长(P<0.05).R2组较C2组逃逸潜伏期延长[逃逸潜伏期分别为R2(14.65±3.83)s,C2(7.84±2.51)s,F=12.773,P<0.01],探索时间缩短(均P<0.01),穿越平台次数减少(P<0.01).S2组与C2组比较,空间探索时间与穿越平台次数均未见显著统计学差异(P>0.05);RAGE表达:与C1组比较S1、R1组mRNA表达水平增高[mRNA表达分别为c1(0.11±0.02),S1(0.56±0.09),R1(0.73±0.14)F=169.447,P<0.01],免疫组化阳性细胞颗粒数增多(P<0.01),S1组与R1组比较蛋白表达差异无统计学意义(P>0.05);与C2组比较,S2组mRNA水平及蛋白表达未见明显差异(P>0.05),但R2组mRNA及免疫组化阳性细胞表达增高,与C2组比较差异有显著意义(均P<0.01).结论 异氟醚导致不同月龄大鼠认知功能改变,尤其对老年大鼠影响显著,可能与海马RAGE表达上调有关.
目的 觀察異氟醚對大鼠海馬高級糖基化終末產物受體(receptor for advanced glycation end products,RAGE)錶達及認知功能的影響.方法 SD雄性老年大鼠(24月齡)45隻,SD雄性成年大鼠(4月齡)45隻,隨機數字錶法分為6組(n=15),老年對照組(C1組),成年對照組(C2組):吸入30%氧氣的空氧混閤氣體對照;老年異氟醚單次吸入組(S1組),成年異氟醚單次吸入組(S2組):1.5%異氟醚單次吸入2h;老年異氟醚多次吸入組(R1組),成年異氟醚多次吸入組(R2組):1.5%異氟醚吸入3次,1次/d,2h/次.各組大鼠吸入處理後1d取8隻行Morris水迷宮進行認知功能測試,其餘大鼠處死取海馬,RT-PCR方法測定RAGE mRNA水平,免疫組織化學方法測定RAGE蛋白錶達.結果 各組大鼠吸入處理過程中生命體徵平穩,血氧飽和度及心率均在正常範圍.C1組穿越平檯次數為(7.30±2.40)次,探索時間為(49.90±6.22)s,S1、R1組與C1組相比穿越平檯的次數減少[穿越平檯次數分彆為S1(3.90±2.42),R1(3.44±2.40),F=7.448,P<0.01],探索時間縮短[探索時間分彆為S1(43.33±7.08)s,R1(39.09±4.56)s,F=7.63,P<0.05],而逃避潛伏期延長(P<0.05).R2組較C2組逃逸潛伏期延長[逃逸潛伏期分彆為R2(14.65±3.83)s,C2(7.84±2.51)s,F=12.773,P<0.01],探索時間縮短(均P<0.01),穿越平檯次數減少(P<0.01).S2組與C2組比較,空間探索時間與穿越平檯次數均未見顯著統計學差異(P>0.05);RAGE錶達:與C1組比較S1、R1組mRNA錶達水平增高[mRNA錶達分彆為c1(0.11±0.02),S1(0.56±0.09),R1(0.73±0.14)F=169.447,P<0.01],免疫組化暘性細胞顆粒數增多(P<0.01),S1組與R1組比較蛋白錶達差異無統計學意義(P>0.05);與C2組比較,S2組mRNA水平及蛋白錶達未見明顯差異(P>0.05),但R2組mRNA及免疫組化暘性細胞錶達增高,與C2組比較差異有顯著意義(均P<0.01).結論 異氟醚導緻不同月齡大鼠認知功能改變,尤其對老年大鼠影響顯著,可能與海馬RAGE錶達上調有關.
목적 관찰이불미대대서해마고급당기화종말산물수체(receptor for advanced glycation end products,RAGE)표체급인지공능적영향.방법 SD웅성노년대서(24월령)45지,SD웅성성년대서(4월령)45지,수궤수자표법분위6조(n=15),노년대조조(C1조),성년대조조(C2조):흡입30%양기적공양혼합기체대조;노년이불미단차흡입조(S1조),성년이불미단차흡입조(S2조):1.5%이불미단차흡입2h;노년이불미다차흡입조(R1조),성년이불미다차흡입조(R2조):1.5%이불미흡입3차,1차/d,2h/차.각조대서흡입처리후1d취8지행Morris수미궁진행인지공능측시,기여대서처사취해마,RT-PCR방법측정RAGE mRNA수평,면역조직화학방법측정RAGE단백표체.결과 각조대서흡입처리과정중생명체정평은,혈양포화도급심솔균재정상범위.C1조천월평태차수위(7.30±2.40)차,탐색시간위(49.90±6.22)s,S1、R1조여C1조상비천월평태적차수감소[천월평태차수분별위S1(3.90±2.42),R1(3.44±2.40),F=7.448,P<0.01],탐색시간축단[탐색시간분별위S1(43.33±7.08)s,R1(39.09±4.56)s,F=7.63,P<0.05],이도피잠복기연장(P<0.05).R2조교C2조도일잠복기연장[도일잠복기분별위R2(14.65±3.83)s,C2(7.84±2.51)s,F=12.773,P<0.01],탐색시간축단(균P<0.01),천월평태차수감소(P<0.01).S2조여C2조비교,공간탐색시간여천월평태차수균미견현저통계학차이(P>0.05);RAGE표체:여C1조비교S1、R1조mRNA표체수평증고[mRNA표체분별위c1(0.11±0.02),S1(0.56±0.09),R1(0.73±0.14)F=169.447,P<0.01],면역조화양성세포과립수증다(P<0.01),S1조여R1조비교단백표체차이무통계학의의(P>0.05);여C2조비교,S2조mRNA수평급단백표체미견명현차이(P>0.05),단R2조mRNA급면역조화양성세포표체증고,여C2조비교차이유현저의의(균P<0.01).결론 이불미도치불동월령대서인지공능개변,우기대노년대서영향현저,가능여해마RAGE표체상조유관.
Objective To explore the effect of isofluranee on receptor for advanced glycation end products (RAGE) expression of hippocampus and learning and memory function in rats. Methods 24-month Sprague-Dawley male rats (n=45) and 4-month Sprague-Dawley male rats (n=45) were randomly divided into six groups with 15 rats each group. Group C1 (aged control group),group C2(adult control group) breath 30% oxygen and air mixed gas; Group S1(single inhalation of isoflurane aged group),Group S2(single inhalation of isoflurane adult group)were anesthetized with 1.5% isoflurane,breath 30% oxygen and air mixed gas for 2h;Group R1(Repeated inhalation of isoflurane aged group), group R2(Repeated inhalation of isoflurane adult group) were anesthetized with 1.5% isoflurane,breath 30% oxygen and air mixed gas 2h a day for three days. Eight rats randomly selected from each group were killed and their hippocampus were immediately isolated for detection of RAGE expression by immunohistochemistry and RT-PCR after accomplished treatment 24h. The remained rats' learning and memory function were assessed using Morris water-maze test. Results The results of Morris water-maze test showed that the times of acerossing the original platform and the time consumption of staying the original platform quadrant was shorter in group S1 and group R1,but the escape latency was longer than group C1(escape latency C1 (9.42± 2.63)s,S1(13.20±3.85)s,R1(17.20±3.44)s, F=12.773, P<0.05). In the group R2,the escape latency was longer but the times of accrossing the original platform and the time consumption of staying the original plat-form quadrant was shorter than group C2 (times of accrossing the original platform C1(7.30±2.40), S1(3.90± 2.42),R1(3.44±2.40), F=7.448, P<0.01).To contrast with the group C2,there were no significant differ-enees in spatial probe test in the group S2(P>0.05). The levels of mRNA and protein of RAGE in hippocampus was significantly higher in group S1 and group R1 than group C1(RAGE mRNA expression C1(0.11±0.02),S1 (0.56±0.09), R1(0.73±0.14), F=179.447, P<0.01). To contrast with the group C2, there were no differ-ences found in the levels of mRNA and protein of RAGE in group S1(P>0.05), but it was higher in the group R2 (RAGE mRNA express C2(0.22±0.04), R2 (0.41±0.08), F=40. 209, P < 0. 01). Conclusion Isoflurane can reduce learning and memory function in both aged and adult rats, but aged rats are particularly significant im-pacted. This effect may be induced by the increase of RAGE expression in hippocampas.
