本文選題：小鼠 + 前腦缺血��； 參考：《山西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的： 腦缺血是腦卒中的一種主要類(lèi)型，嚴(yán)重危害病人的健康，至今并無(wú)良好的治療手段。降壓藥AT1受體阻斷劑可以通過(guò)控制高血壓這一腦卒中的高危因素，而減少腦卒中的發(fā)生。研究還發(fā)現(xiàn)腦缺血后腦內(nèi)血管緊張素系統(tǒng)發(fā)生了變化，而且改變腦內(nèi)血管緊張素系統(tǒng)成分也相應(yīng)對(duì)腦缺血的損傷產(chǎn)生作用。眾多動(dòng)物實(shí)驗(yàn)證實(shí)了AT1受體阻斷劑對(duì)腦缺血再灌的保護(hù)作用，并探討了其在神經(jīng)元凋亡、氧化應(yīng)激反應(yīng)、炎癥反應(yīng)等方面的可能機(jī)制，但研究局限于再灌前期。本實(shí)驗(yàn)為進(jìn)一步探討AT1受體阻斷劑氯沙坦對(duì)小鼠前腦缺血再灌后期有無(wú)保護(hù)作用。由于星形膠質(zhì)細(xì)胞在腦缺血再灌后期對(duì)神經(jīng)再生和功能恢復(fù)有抑制作用，，相關(guān)研究也提示AT1受體對(duì)星形膠質(zhì)細(xì)胞有抑制作用。故本實(shí)驗(yàn)將對(duì)這一作用進(jìn)行研究。 方法： 將正常小鼠隨機(jī)分為多個(gè)組，選擇0.5mg/kg、1mg/kg和5mg/kg三個(gè)劑量的氯沙坦鉀經(jīng)腹腔注射給藥，對(duì)照組給予生理鹽水。通過(guò)阻斷雙側(cè)頸總動(dòng)脈60min建立前腦缺血模型。給藥的第15d，給予腦缺血或假手術(shù)處理，手術(shù)后仍給藥；比較再灌后各組的體重和運(yùn)動(dòng)功能的變化；再灌16d時(shí)對(duì)各組存活小鼠進(jìn)行水迷宮學(xué)習(xí)記憶實(shí)驗(yàn)；再灌21d時(shí)，對(duì)各組小鼠灌流取腦、冰凍切片、甲苯胺藍(lán)染色、免疫熒光染色，觀察紋狀體、海馬CA1區(qū)神經(jīng)元損傷情況及海馬CA1區(qū)星形膠質(zhì)細(xì)胞的改變。 結(jié)果： 再灌1d后前腦缺血組小鼠體重即出現(xiàn)下降，給予1mg/kg氯沙坦在再灌3、7、14及21d后顯著提高小鼠的體重恢復(fù)程度。但0.5mg/kg和5mg/kg兩個(gè)劑量無(wú)明顯改善。假手術(shù)組小鼠給藥前后體重增加的程度無(wú)顯著差異。 再灌3d及21d后，前腦缺血組小鼠在旋轉(zhuǎn)棒上停留的時(shí)間顯著低于對(duì)照組，給予1mg/kg氯沙坦顯著提高小鼠在旋轉(zhuǎn)棒上停留的時(shí)間。0.5mg/kg和5mg/kg兩個(gè)劑量并無(wú)明顯改善。假手術(shù)組小鼠給藥前后在旋轉(zhuǎn)棒上停留的時(shí)間增加，但組間增加的程度無(wú)顯著差異。 再灌16d進(jìn)行水迷宮實(shí)驗(yàn)。訓(xùn)練第3d和第4d時(shí)，前腦缺血組小鼠相比于對(duì)照組找到平臺(tái)的潛伏期顯著延長(zhǎng)，給予1mg/kg氯沙坦顯著縮短小鼠找到平臺(tái)的潛伏期，而給予5mg/kg氯沙坦僅在訓(xùn)練第4d顯著縮短小鼠找到平臺(tái)的潛伏期。0.5mg/kg劑量無(wú)明顯改善。給予1mg/kg氯沙坦的假手術(shù)組小鼠在訓(xùn)練階段找到平臺(tái)的潛伏期與對(duì)照組無(wú)顯著差異。 再灌21d后，前腦缺血組小鼠相比于對(duì)照組在紋狀體和海馬CA1區(qū)可見(jiàn)明顯損傷。前腦缺血組小鼠相比于對(duì)照組，紋狀體和海馬CA1區(qū)神經(jīng)元密度都有顯著下降，給予1mg/kg氯沙坦顯著逆轉(zhuǎn)了紋狀體和海馬CA1區(qū)神經(jīng)元的損傷，而0.5mg/kg則僅顯著逆轉(zhuǎn)海馬CA1區(qū)神經(jīng)元的損傷。Bccao+Los(5mg/kg)組對(duì)神經(jīng)元密度沒(méi)有顯著改善作用。 另外，再灌21d后，前腦缺血組相比于對(duì)照組，顯著增加海馬CA1區(qū)GFAP的表達(dá)和GFAP陽(yáng)性細(xì)胞密度，給予1mg/kg氯沙坦顯著抑制了這一增加。 結(jié)論： 氯沙坦能夠促進(jìn)小鼠前腦缺血再灌后體重與運(yùn)動(dòng)功能的恢復(fù)，并改善再灌后期空間學(xué)習(xí)記憶能力的降低和神經(jīng)元的缺失。氯沙坦對(duì)再灌后期星形膠質(zhì)細(xì)胞激活和增殖的顯著抑制，可能是其在再灌后期發(fā)揮神經(jīng)保護(hù)作用的靶點(diǎn)之一。
[Abstract]:Purpose :

Cerebral ischemia is one of the main types of cerebral apoplexy , which is a serious harm to the health of patients . It has not been used to treat cerebral ischemia .

Method :

Normal mice were randomly divided into a plurality of groups , 0.5 mg / kg , 1 mg / kg and 5 mg / kg of losartan potassium were injected intraperitoneally to the control group .
comparing the weight of each group and the change of exercise function after re - irrigation ;
water maze learning and memory experiment was carried out on the survival mice of each group at the time of reperfusion ;
Twenty - two days later , the brain , frozen section , methylene blue staining and immunofluorescence staining were performed on each group of mice to observe the damage of neurons in the striatum and hippocampus CA1 region and the changes of astrocytes in CA1 region of hippocampus .

Results :

After reperfusion , the weight of mice in the cerebral ischemia group decreased , and the weight recovery of mice was significantly improved after 3 , 7 , 14 and 21 days after reperfusion . However , the dosage of 0 . 5mg / kg and 5 mg / kg did not improve significantly .

After 3 d and 21 d reperfusion , the time of stay on the rotating rod was significantly lower than that of the control group , and the dose of 1 mg / kg losartan significantly increased the stay time of the mice on the rotating rod . The dose of 0.5 mg / kg and 5 mg / kg did not improve significantly . The time of stay on the rotating rod was increased before and after the administration of the sham operation group , but there was no significant difference between the groups .

At the 3rd and 4th day of training , the latency of the platform was significantly shortened compared with the control group , and the latency of the platform was significantly shortened compared with the control group .

Compared with the control group , the density of neurons in the striatum and the CA1 region of the hippocampus decreased significantly compared with the control group , and 1 mg / kg losartan significantly reversed the damage of the neurons in the striatum and the CA1 region of the hippocampus , while 0.5 mg / kg only significantly reversed the damage of the neurons in the CA1 region of the hippocampus .

In addition , compared with the control group , the expression of GFAP and GFAP - positive cell density in the CA1 region of the hippocampus were significantly increased after 21 days of reperfusion , and the increase was significantly inhibited by the administration of 1 mg / kg losartan .

Conclusion :

losartan can promote the recovery of body weight and exercise function after cerebral ischemia reperfusion in mice , and improve the reduction of spatial learning and memory capacity at the later stage of reperfusion and the loss of neurons , and losartan can inhibit the activation and proliferation of astrocytes in the later stage of reperfusion , and may be one of the targets in which the nerve protection function is exerted in the later period of reperfusion .

【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R743.3

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