Nutlin-3a緩釋微球促大鼠脊髓損傷后功能恢復(fù)的實(shí)驗(yàn)研究
本文選題:脊髓損傷 切入點(diǎn):微球 出處:《重慶醫(yī)科大學(xué)》2017年碩士論文 論文類型:學(xué)位論文
【摘要】:目的:探討Nutlin-3a-PLGA微球?qū)Υ笫蠹顾钃p傷后運(yùn)動(dòng)功能恢復(fù)的影響。方法:采用單乳化法制備Nutlin-3a-PLGA微球。健康雌性成年SD大鼠采用隨機(jī)數(shù)字表法分為單純損傷組、生理鹽水微球治療組和Nutlin-3a-PLGA微球治療組,每組12只,并對(duì)T10脊髓進(jìn)行右半橫斷損傷;另取3只大鼠進(jìn)行正常鉻化青染色。單純損傷組僅行脊髓右半橫斷損傷而不給予治療,生理鹽水微球治療組術(shù)后予以生理鹽水微球治療,Nutlin-3a-PLGA微球治療組術(shù)后予以Nutlin-3a-PLGA微球治療。術(shù)后2、4周行鉻化青染色觀察脊髓脫髓鞘情況,術(shù)前1天,術(shù)后2、3、4周行Catwalk步態(tài)分析正常步序比、站立時(shí)間、足印平均強(qiáng)度、兩后爪腳間距離以及相對(duì)足印距離5個(gè)時(shí)間-空間參數(shù)評(píng)價(jià)大鼠運(yùn)動(dòng)功能變化。結(jié)果:傷后4周與單純損傷組和生理鹽水微球治療組比較,Nutlin-3a-PLGA微球治療組鉻化青染色顯示脫髓鞘病變較輕,髓鞘排列較為緊密。與術(shù)前比較,術(shù)后2周單純損傷組和生理鹽水微球治療組Catwalk步態(tài)分析各項(xiàng)行為學(xué)參數(shù)差異有統(tǒng)計(jì)學(xué)意義;Nutlin-3a-PLGA微球治療組正常步序比、兩后爪腳間距離以及左、右相對(duì)足印距離差異有統(tǒng)計(jì)學(xué)意義,左后肢站立時(shí)間和前肢足印平均強(qiáng)度差異無(wú)統(tǒng)計(jì)學(xué)意義。與單純損傷組和生理鹽水微球治療組比較,Nutlin-3a-PLGA微球治療組傷后2周左后肢站立時(shí)間和前肢足印平均強(qiáng)度均降低,正常步序比增加;傷后4周兩后爪腳間距離減小,左、右相對(duì)足印距離顯著減小。結(jié)論:Nutlin-3a-PLGA微球局部作用能夠促進(jìn)脊髓半橫斷損傷大鼠運(yùn)動(dòng)功能的恢復(fù),對(duì)損傷節(jié)段軸突的再生可能有促進(jìn)作用。
[Abstract]:Objective: to investigate the effect of Nutlin-3a-PLGA microspheres on motor function recovery after spinal cord injury in rats. Methods: Nutlin-3a-PLGA microspheres were prepared by single emulsification. Normal saline microspheres treatment group and Nutlin-3a-PLGA microsphere treatment group, each group, 12 rats, and T10 spinal cord right half transection injury, another 3 rats were taken for normal chromocystin staining. The simple injury group only right half spinal cord transection injury without treatment, The saline microspheres group was treated with Nutlin-3a-PLGA microspheres after operation, and the Nutlin-3a-PLGA microspheres were treated with Nutlin-3a-PLGA microspheres. Catwalk gait analysis was performed at 2 ~ 3 ~ 4 weeks postoperatively. The normal step order ratio, standing time, and the average strength of footprints were analyzed. Results: the changes of motor function in rats were evaluated by 5 time and space parameters of the distance between the feet of the two posterior claws and the relative footprint distance. Results: Nutlin-3a-PLGA microsphere treatment group was compared with the simple injury group and the saline microsphere treatment group at 4 weeks after the injury and the chrominated blue staining was compared with that in the Nutlin-3a-PLGA microsphere treatment group. Color showed that demyelinating lesions were mild. Compared with before operation, there were significant differences in Catwalk gait analysis between simple injury group and saline microsphere treatment group 2 weeks after operation. There were significant differences in normal step ratio, distance between two posterior claws and feet, left, left, and so on in Nutlin-3a-PLGA microsphere treatment group. The difference of right relative footprint distance is statistically significant. There was no significant difference in the standing time of left hind limb and the average strength of forefoot imprint. Compared with the simple injury group and the saline microsphere treatment group, the standing time of left hind limb and the average strength of forefoot imprint decreased in the Nutlin-3a-PLGA microsphere treatment group 2 weeks after injury. The normal step sequence ratio increased, the distance between the two paws and feet decreased, and the distance between left and right foot marks decreased significantly 4 weeks after injury. Conclusion the local action of the microspheres at 1: Nutlin-3a-PLGA can promote the recovery of motor function in rats with spinal cord hemitranverse injury. It may promote the regeneration of injured segmental axons.
【學(xué)位授予單位】:重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R651.2
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