胰島素抵抗大鼠前列腺微血管新生的實(shí)驗(yàn)研究

　　[摘要] 目的 探討2型糖尿病胰島素抵抗大鼠前列腺微血管新生與良性前列腺增生癥發(fā)生發(fā)展的關(guān)系。 方法 ①正常對照組大鼠（Normal組，n=15）：8～10周齡正常雄性Wistar大鼠；②單純良性前列腺增生組大鼠（BPH組，n=15）：手術(shù)去勢后外源性給予高劑量雄激素；③胰島素抵抗前列腺增生組大鼠（GK+BPH組，n=15）：8～10周齡自發(fā)型非肥胖型2型糖尿病Wistar大鼠（GK大鼠），手術(shù)去勢后外源性給予高劑量雄激素；④胰島素抵抗前列腺增生血糖干預(yù)組大鼠（GK+BPH+PH組，n=15）：8～10周齡GK大鼠手術(shù)去勢后外源性給予高劑量雄激素，同時(shí)給予鹽酸吡格列酮灌胃。光化學(xué)法檢測大鼠空腹血糖水平；ELISA雙抗體夾心法檢測大鼠血清胰島素水平及前列腺DHT含量；real-time PCR法檢測大鼠前列腺VEGF、Ang-1、Ang-2 mRNA表達(dá)量；免疫組化S-P法檢測前列腺組織CD31表達(dá)并根據(jù)陽性結(jié)果計(jì)數(shù)MVD。 結(jié)果 ①GK+BPH、GK+BPH+PH組空腹血糖水平及胰島素抵抗指數(shù)高于Normal組及BPH組（P<0.05）；GK+BPH組指標(biāo)高于GK+BPH+PH組（P<0.05）；Normal組及BPH組上述指標(biāo)差異無統(tǒng)計(jì)學(xué)意義（P>0.05）。BPH組、GK+BPH組、GK+BPH+PH組前列腺組織中DHT含量與Normal組相比明顯增高（P<0.05）；GK+BPH組、GK+BPH+PH組高于BPH組，且GK+BPH組高于GK+BPH+PH組（P<0.05）；②各組前列腺組織中VEGF、Ang-1、Ang-2 mRNA表達(dá)量及MVD計(jì)數(shù)結(jié)果為GK+BPH組>GK+BPH+PH組>BPH組>Normal組，組間差異有統(tǒng)計(jì)學(xué)意義（P<0.05）；③GK+BPH組、GK+BPH+PH組大鼠前列腺組織中DHT含量與胰島素抵抗指數(shù)呈正相關(guān)（P<0.05），相關(guān)性顯著。 結(jié)論 2型糖尿病伴胰島素抵抗時(shí)，可通過增加前列腺組織DHT的含量從而上調(diào)VEGF、Ang-1、Ang-2的表達(dá)，促進(jìn)前列腺組織局部血管新生以加速良性前列腺增生癥的進(jìn)展。
　　[關(guān)鍵詞] 胰島素抵抗；前列腺增生癥；血管內(nèi)皮生長因子；血管生成素；微血管密度
　　[中圖分類號] R691.9 [文獻(xiàn)標(biāo)識碼] A [文章編號] 1673-9701（2018）08-0035-05
　　Experiment of microvascular angiogenesis of prostate in rats with insulin resistance
　　MI Yang1 YUAN Xiaobin2 ZHANG Bin2 WANG Dongwen2 ZHANG Xuhui2
　　1.First School of Clinical Medicine of Shanxi Medical University， Taiyuan 030001， China； 2.Department of Urology， First Hospital of Shanxi Medical University， Taiyuan 030001， China
　　[Abstract] Objective To investigate the association between the microvascular angiogenesis and the occurrence and progress of benign prostatic hyperplasia（BPH） in type-2 diabetic rats with insulin resistance（IR）. Methods ①Rats of normal group（n=15）： normal male Wistar rats aged 8 to 10 weeks. ②Rats of BPH group（n=15）： high-dose exogenous androgen was given after surgical castration. ③Rats with IR and BPH（GK+BPH） group（n=15）： high-dose exogenous androgen was given to spontaneous non-obese type-2 diabetic Wistar rats（GK rats） aged 8 to 10 weeks. ④Rats of IR and BPH with blood glucose intervened（GK+BPH+PH） group（n=15）： high-dose exogenous androgen was given to GK rats aged 8 to 10 weeks and pioglitazone hydrochloride was given by intragastric administration. The level of fasting blood glucose in rats was assessed by photochemical method. The levels of serum insulin and DHT in prostate of rats were assessed by double antibody sandwich ELISA. The expression of VEGF， Ang-1 and Ang-2 in prostate of rats was assessed by real-time. The expression of CD31 in prostate tissue was assessed by the S-P immunohistochemical method and MVD was counted based on the positive results. Results ①The level of fasting blood glucose and the IR index in GK+BPH group and GK+BPH+PH group were higher than those in normal group and BPH group（P<0.05）. Those in GK+BPH group were higher than GK+BPH+PH group（P<0.05） while there was no statistical difference between normal group and BPH group（P>0.05）. The level of DHT in the prostate tissue of BPH group， GK+BPH group and GK+BPH+PH group was higher than that in normal group（P<0.05）. That in GK+BPH group and GK+BPH+PH group was higher than BPH group and that in GK+BPH group was higher than GK+BPH+PH group（P<0.05）. ②The levels of mRNA of VEGF， Ang-1 and Ang-2 and the MVD count were： GK+BPH group>GK+BPH+PH group>BPH group>Normal group， with statistical differences between each other（P<0.05）. ③The level of DHT in the prostate tissue of GK+BPH group and GK+BPH+PH group was significantly and positively associated with the IR index（P<0.05）. Conclusion When IR occurred in type-2 diabetes， the level of DHT in prostate tissue could be increased to up-regulate the expression of VEGF， Ang-1 and Ang-2 and promote the microvascular angiogenesis in prostate tissue so as to accelerate the progress of benign prostatic hyperplasia.

相關(guān)熱詞搜索：微血管 胰島素 前列腺 抵抗 實(shí)驗(yàn)研究