间充质干细胞高表达ILK对糖尿病膀胱病的疗效及其机制研究

Diabetic cystopathy (DCP) is the most common disorder with chronic diabetes，which seriously reduces the quality of life ，but it is still lack of the treatment.Bladder destrusor dysfunction is defined as impaired endothelium because of ischemia and polyneuropathy in response to hyperglycemia. The main pathogeny of DCP is atrophy of detrusor muscle,for the neuronal non-regenerative characteristic, consequently improving the blood suppply of destrusor, promoting the proliferation of functional cells and repairing the function of nerve are becoming the key treatment of DCP. In recent years, as a hopeful research direction, mesenchymal stem cells(MSCs) has received significant attention, nevertheless the low efficiency of differentiation and less colonization of the simply transplanted MSCs are the main obstacle for further application. Integrin-linked kinase(ILK) is a multifunctional Ser / Thr protein kinase, it plays a key role in angiogenesis and matrix-endothelial cell interactions,endothelial and extracellular matrix -mediated signaling, cell survival and proliferation. In preliminary experiments, high regulation of ILK was proved to promote the detrusor cell proliferation and angiogenesis after ILK transfection into the MSCs. On this basis, our study is aimed to investigate the efficacy of the locally transplanted ILK-MSCs on the treatment of DCP through the detection of histological and functional parameters. The overexpression of ILK is expected to promote the colonization of MSCs, angiogenesis and cell proliferation, meanwhile, so as the neural protective effect of several cytokines secreted by MSCs. In a word, this research is designed to improve the efficacy of transplanted MSCs on the treatment of DCP and explore the treatment mechanism of locally transplanted ILK-MSCs.

糖尿病膀胱病日益高发，严重影响患者生活质量，迄今仍是治疗难点。糖尿病膀胱病关键致病环节是高血糖导致的缺血及神经病变引起的逼尿肌萎缩，但神经无法再生，故改善逼尿肌血供，促进细胞增殖，改善神经功能是糖尿病膀胱病治疗关键。间充质干细胞移植为此类疾病带来新的希望，但单纯MSCs(间充质干细胞)移植的分化效率低、定植少等缺点。整合素链接激酶(ILK) 是一个多功能的Ser/Thr蛋白激酶，在血管新生、细胞增殖发挥着重要的作用。本项目拟在前期预实验高表达ILK促进血管新生及细胞增殖基础上，通过组织学及功能学指标评估逼尿肌局部移植ILK-MSCs对糖尿病膀胱病的疗效。希望通过ILK高表达促进MSCs定植、血管新生及细胞增殖；同时放大MSCs所分泌的多种细胞因子对神经元保护效应，进而提高MSCs移植治疗DCP（糖尿病膀胱病）的效果，并进一步探讨ILK-MSCs膀胱逼尿肌移植治疗DCP的相关机制。

糖尿病膀胱病日益高发，严重影响患者生活质量，迄今仍是治疗难点。糖尿病膀胱病关键致病环节是高血糖导致的缺血及神经病变引起的逼尿肌萎缩，但神经无法再生，故改善逼尿肌血供，促进细胞增殖，改善神经功能是糖尿病膀胱病治疗关键。间充质干细胞移植为此类疾病带来新的希望，但单纯MSCs(间充质干细胞)移植的分化效率低、定植少等缺点。整合素链接激酶(ILK) 是一个多功能的Ser/Thr蛋白激酶，在血管新生、细胞增殖发挥着重要的作用。本项目拟在前期预实验高表达ILK促进血管新生及细胞增殖基础上，通过组织学及功能学指标评估逼尿肌局部移植ILK-MSCs对糖尿病膀胱病的疗效。希望通过ILK高表达促进MSCs定植、血管新生及细胞增殖；同时放大MSCs所分泌的多种细胞因子对神经元保护效应，进而提高MSCs移植治疗DCP（糖尿病膀胱病）的效果，并进一步探讨ILK-MSCs膀胱逼尿肌移植治疗DCP的相关机制。