Adv Mater:中国科大等在克服肝脏移植排斥研究中取得进展

2018-10-14 佚名 中国科学技术大学

研究表明,活化的T细胞会高表达蛋白质酪氨酸激酶(PTK),而在蛋白质酪氨酸激酶的大家族中,淋巴细胞特异性的蛋白质酪氨酸激酶(Lck)被发现在肝脏移植时最高表达而且分泌到细胞外。Lck又有着一个特异性磷酸化的底物Glu-Tyr。

9月25日,国际学术期刊《先进材料》在线发表了中国科学技术大学化学与材料科学学院教授梁高林课题组与南京医科大学的合作研究成果,文章标题为Immune Responsive Release of Tacrolimus to Overcome Organ Transplant Rejection。该文章报道了一种免疫响应释放他克莫司的策略,在克服肝脏移植排斥研究中取得新进展(Adv. Mater. 2018, 201805018)。

移植排斥是器官移植面临的最大问题。临床上克服移植排斥的方法是,在病人手术做完后直接服用免疫抑制剂(例如,他克莫司)来抑制器官移植引起的T细胞活化。然而,直接服用大剂量的免疫抑制剂可能给病人带来严重的毒副作用。

研究表明,活化的T细胞会高表达蛋白质酪氨酸激酶(PTK),而在蛋白质酪氨酸激酶的大家族中,淋巴细胞特异性的蛋白质酪氨酸激酶(Lck)被发现在肝脏移植时最高表达而且分泌到细胞外。Lck又有着一个特异性磷酸化的底物Glu-Tyr。基于这个特点,梁高林课题组设计了Nap-Phe-Phe-Glu-Tyr-OH (1)和Nap-D-Phe-D-Phe-Glu-Tyr-OH (2)两种水凝胶来包裹他克莫司。他们与南京医科大学肝脏移植专家、中国工程院院士王学浩团队以及分析中心博士王富强团队合作,把包裹药物的水凝胶涂于肝脏移植伤口表面。移植排斥发生时,活化的T细胞释放出Lck,Lck磷酸化水凝胶的Glu-Tyr导致解胶释放他克莫司来抑制活化的T细胞(见下图)。



大鼠肝脏移植实验表明,采用临床策略口服他克莫司的大鼠平均存活13天,而采用水凝胶“智能”免疫响应释放他克莫司的大鼠平均存活22天。研究者希望这种“智能”免疫响应释放药物的策略尽快推广至临床使用。

该论文并列第一作者为南京医科大学博士吴金道和中国科大化学与材料科学学院博士生郑珍。梁高林为最后通讯作者。

该课题得到国家杰出青年科学基金基金委创新群体项目等资助。

原始出处:Wu J, Zheng Z, Chong Y, et al. Immune Responsive Release of Tacrolimus to Overcome Organ Transplant Rejection. Adv Mater. 2018 Sep 25:e1805018.

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    2019-06-04 jml2009
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    2018-10-19 13718711b3m

    非常不错的实战经验,值得借鉴与学习,获益匪浅,谢谢分享!

    0

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    2018-10-15 明月清辉

    谢谢分享,学习了

    0

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    2018-10-15 phoebeyan520

    学习了

    0

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