TAT-SOD脂质体对UC模型大鼠的口服治疗作用
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Therapeutic Effect of Orally Administered TAT-SOD Liposome on UC Rat Models
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    摘要:

    氧化应激是造成溃疡性结肠炎(UC)的重要原因之一,而超氧化物歧化酶(SOD)是调控氧化应激的基本分子。为了探究TAT-SOD脂质体对UC模型大鼠的口服治疗作用,作者利用乙醇沉淀和大孔树脂分离的方法,从基因重组毕赤酵母菌发酵液中分离纯化TAT-SOD;利用TritonX-114相分离法,去除其细菌内毒素;利用逆向蒸发法,制备TAT-SOD脂质体;利用DSS诱导构建UC模型大鼠,经灌胃给药,通过DAI评分、结肠密度、组织切片、血清SOD酶活、血清脂多糖含量,评价其治疗效果。结果表明:初步分离获得TAT-SOD,比活为11 003 U/mg;TritonX-114对内毒素的去除率为99.30%;成功制备TAT-SOD脂质体,经体外模拟消化液处理,其酶活回收率为81.80%;动物实验中,SOD给药组与模型组相比,DAI评分均显著降低(P<0.05),且TAT-SOD脂质体组的评分最好;结肠密度和组织切片观察发现,结肠组织损伤情况均明显改善,且TAT- SOD脂质体组的改善最好;血清中SOD酶活均显著提高(P<0.05),且TAT-SOD脂质体组的酶活最高;血清中LPS含量无显著差异。这些表明,TAT-SOD脂质体对DSS诱导UC模型大鼠有良好的口服治疗效果,有望为UC的辅助治疗提供新的选择。

    Abstract:

    Oxidative stress is one of the major causes of ulcerative colitis(UC), and superoxide dismutase(SOD) is the basic molecule to regulate oxidative stress. This study investigated the therapeutic effect of oral administered TAT-SOD liposome (L-TAT-SOD) on UC rat models.The isolated and purified TAT-SOD from the fermentation broth of recombinant Pichia pastoris was achieved by ethanol precipitation, macroporous resin column chromatography and TritonX-114 phase separation. Subsequently, the L-TAT-SOD was prepared by reverse evaporation. Finally, the UC rat models were established by dextran sodium sulfate (DSS) induction and administered by intragastric administration. The anti-UC effect of L-TAT-SOD was evaluated by DAI score, colon density, damage of colon tissue, serum SOD enzyme activity and serum lipopoly saccharide content.Results showed that: The specific activity of isolated TAT-SOD was 11 003 U/mg. The recovery rates of enzyme activity of successfully prepared L-TAT-SOD were about 80% and 90% in simulated gastric and intestinal juice, respectively. In anti-UC experiments, all administered groups had lower DAI scores(P<0.05) than that of the model group. In contrast, the L-TAT-SOD group had the lowest DAI score.The results of colon density and tissue section showed that the damaged colon tissue was significantly repaired in all administered groups, and the L-TAT-SOD group performed best.Meanwhile, the serum SOD enzyme activity was significantly increased in all groups(P<0.05), and the activity in L-TAT-SOD group was highest. However, there was no significant difference in serum lipopolysaccharide content in each group. The oral administered L-TAT-SOD is confirmed with a beneficial therapeutic effect on DSS-induced UC rat models, expected to be a new option for the adjuvant therapy of UC.

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周建森,周秋婷,叶芬,林春通,刘航琪,刘树滔. TAT-SOD脂质体对UC模型大鼠的口服治疗作用[J].食品与生物技术学报,2020,39(10):26-33.

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  • 在线发布日期: 2021-01-15

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