BPH伴DM或IFG患者的尿流动力学分析及格列卫对酪氨酸激酶高选择性的基础研究

发布时间：2018-04-22 09:04

本文选题：前列腺增生 + 糖尿病　；参考：《大连医科大学》2017年硕士论文

【摘要】：目的:研究探讨良性前列腺增生伴糖尿病或空腹血糖调节受损患者的尿流动力学改变,对这两类患者提出合理的治疗和处理。方法:本研究选取从2014年10月~2016年10月在大连医科大学附属第二医院泌尿外科行经尿道前列腺电切术或经尿道前列腺剜除术,术后病理诊断为良性前列腺增生并且术前行尿流动力学检查的患者163例,分为前列腺增生合并糖尿病40例(研究组1)、前列腺增生合并空腹血糖调节受损(IFG)22例(研究组2),单纯前列腺增生101例(对照组)。比较各组患者尿流动力学各项检查结果。结果:糖尿病组和对照组的不稳定膀胱率比较,P值0.02;空腹血糖调节受损组和对照组的不稳定膀胱率比较,P值0.025;糖尿病组和空腹血糖调节受损组的不稳定膀胱率比较,P值0.499。对糖尿病组和对照组的Qmax、Pdet at Qmax、Pdet max、PVR、FDV检测指标进行比较,P值分别为0.001、0.202、0.330、0.001、0.002;对空腹血糖调节受损组和对照组的Qmax、Pdet at Qmax、Pdet max、PVR、FDV检测指标进行比较,P值分别为0.008、0.171、0.153、0.191、0.012;对糖尿病组和空腹血糖调节受损组的Qmax、Pdet at Qmax、Pdet max、PVR、FDV检测指标进行比较,P值分别为0.006、0.165、0.052、0.005、0.001。结论:高血糖和前列腺增生都对膀胱功能影响方面具有协同作用。对于BPH伴糖尿病或空腹血糖调节受损患者应该引起重视,积极治疗BPH的同时尽早采取合理有效的治疗措施控制好血糖水平。在治疗癌症方面蛋白激酶是重要的药物靶点。格列卫(Abl激酶的特殊抑制剂)这种药物区分Abl和其它酪氨酸激酶(例如Src)的能力被广泛研究但是没有很大成功。本研究中,我们运用分子动力学模拟是基于Abl、Src和它们共同祖先(ANC-AS)以及构建的两个突变体系(AS→Abl和AS→Src)的晶体结构。MD模拟揭示了在AS→Abl体系磷酸结合位点的loop(P-loop)发生了重要改变。DCCM的结果揭示了在AS→Abl体系突变导致反相关运动增加。动态网络分析提示P-loop在AS→Abl体系建立了特殊的连接,同时这种连接在AS→Src体系中不存在。结合自由能计算揭示了格列卫对于AS→Abl突变体的亲和力接近于Abl,同时对AS→Src突变体的亲和力降低到接近于Src。个体残基贡献发现不同主要位于P-loop区域。本研究有助于理解格列卫对于酪氨酸激酶的选择性。
[Abstract]:Objective: to investigate the changes of urodynamics in patients with benign prostatic hyperplasia (BPH) with diabetes mellitus or impaired fasting blood glucose regulation (FBG). Methods: from October 2014 to October 2016, transurethral resection or transurethral enucleation of the prostate was performed in the Department of Urology, second affiliated Hospital of Dalian Medical University. There were 163 patients with benign prostatic hyperplasia diagnosed as benign prostatic hyperplasia and underwent urodynamic examination before operation. There were 40 cases of benign prostatic hyperplasia with diabetes mellitus (study group 1), 22 cases of prostatic hyperplasia with impaired fasting blood glucose regulation (study group 2) and 101 cases of simple prostatic hyperplasia (control group). The results of urodynamic examination were compared in each group. Results: the unstable bladder rate was 0.02 in diabetic group and control group, 0.025 in impaired fasting glucose regulation group and 0.025 in control group, and 0.499 in diabetic group and impaired fasting glycemic regulation group. The results of QmaxPdet at QmaxPdet at QmaxPdet maxPdet in diabetes group and control group were compared with those of control group (P = 0.001) and control group (P = 0.001), respectively (P = 0.001, 0.202, 0.330, 0.001, 0.002; P = 0.008, 0.171, 0.1530.191, 0.012, respectively, respectively), and QmaxPdet at QmaxPdet at maxPdet maxPVRFDV, respectively, in impaired fasting blood glucose regulation group and control group, respectively, in diabetic group and control group, in the diabetic group and the control group, the values of QmaxPdet at QmaxPdet and QmaxPdet in control group were compared with those in control group. The values of Pdet at QmaxPdet and PVRV FDV in impaired glucose regulation group were 0. 006 ~ 0. 165 ~ 0. 052 ~ 0. 005 ~ 0. 001, and P = 0. 006 ~ 0. 165 ~ 0. 05 ~ 0. 05 ~ 0. 005 ~ 0. 001, respectively. Conclusion: hyperglycemia and prostatic hyperplasia have synergistic effects on bladder function. Attention should be paid to patients with BPH accompanied by diabetes mellitus or impaired fasting blood glucose regulation. Reasonable and effective treatment measures should be taken to control blood glucose level as early as possible while actively treating BPH. Protein kinase is an important drug target in the treatment of cancer. The ability of the drug to distinguish Abl from other tyrosine kinases (such as SRC) has been extensively studied but has not been very successful. In this study, The molecular dynamics simulation is based on the crystal structure of Ablsrc and their common ancestor ANC-ASand two mutant systems, as Abl and as SRC). MD simulation shows that the loop-P-loop-loop-loop of phosphoric acid binding site in as Abl system is heavy. To change the results of .DCCM, it is revealed that mutations in as / Abl system lead to an increase in inversely correlated motion. Dynamic network analysis indicates that P-loop has established a special connection in as / Abl system, and this kind of connection does not exist in as / Src system. Combined with the calculation of free energy, the affinity of Glewey to as Abl mutant was close to that of Abll, while the affinity to as Src mutant was reduced to close to that of Srcc. Individual residual contribution was found to be mainly located in the P-loop region. This study is helpful to understand Glevir's selectivity to tyrosine kinase.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R697.3;R587.2;R694

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