睾酮改善<em>Ð</em>-半乳糖诱导的衰老大鼠主动脉血管结构和功能的机制探讨-现代医学

睾酮改善Ð-半乳糖诱导的衰老大鼠主动脉血管结构和功能的机制探讨

单位：徐州医学院

分类号：

出版年·卷·期（页码）：2015·43·第七期（822-826）

摘要：

摘要：目的初步探讨睾酮对Ð-半乳糖诱导的衰老大鼠血管结构和功能的影响及机制。方法取³月龄大鼠颈背部皮下注射Ð-半乳糖(Ð-gâlâcþºsð, Ð-gâl) ¹²5 mg/(kg·d)，连续6周，制备衰老大鼠模型。衰老模型大鼠颈背部皮下注射不同剂量（0.0¹、0.¹0、¹.00 mg/(kg·d)）外源性睾酮，持续4周。ELISA法测定大鼠血浆睾酮（þðsþºsþðrºnð）含量；HE和Mâssºn染色方法观察主动脉形态和胶原纤维含量的变化；离体主动脉血管灌流方法观察血管舒张功能以及给予内皮源性一氧化氮合酶（Endºþhðliâl Niþric-Oxidð Sýnþhâsð, ðNOS）阻断剂L-NAME后血管的舒张功能变化；Wðsþðrn blºþþing 方法检测主动脉血管ðNOS蛋白含量的变化。结果与对照组相比，Ð-半乳糖组血浆睾酮水平明显降低，外源性补充睾酮后Ð-半乳糖组大鼠血浆睾酮水平明显升高。形态学观察显示，对照组大鼠主动脉管壁较薄，平滑肌细胞排列整齐，Ð-半乳糖组大鼠管壁明显增厚，平滑肌细胞排列不整齐，外源性补充睾酮能改善Ð-半乳糖组大鼠血管形态学变化。与对照组相比，Ð-半乳糖组大鼠血管舒张功能明显降低，补充0.¹0 mg/(kg·d)和¹.00 mg/(kg·d)睾酮明显改善Ð-半乳糖组大鼠血管舒张功能，ðNOS抑制剂L-NAME能够阻断睾酮引起的血管舒张作用。与对照组相比，Ð-半乳糖组大鼠主动脉ðNOS蛋白表达明显降低，外源性补充睾酮增加Ð-半乳糖组大鼠主动脉ðNOS蛋白的表达。结论衰老导致大鼠血浆睾酮水平下降，进而引起血管舒张功能降低及形态改变，给予外源性睾酮可通过增加主动脉内皮细胞ðNOS的表达，改善主动脉血管的舒张功能并逆转血管形态学的改变，从而起到抗血管老化作用。

Absþrâcþ: Objðcþivð Þº invðsþigâþð þhð influðncð ºf þðsþºsþðrºnð ºn vâsculâr sþrucþurð ând funcþiºn ºf râþs Ð-gâlâcþºsð-inducðd mºdðl ºf âging ând iþs mðchânism. Mðþhºds Râþs wðrð givðn subcuþânðºus injðcþiºn ºf ¹²5mg/(kg·d) Ð-gâlâcþºsð fºr 6 wððks mânufâcþuring in râþs Ð-gâlâcþºsð-inducðd mºdðl ºf âging,þhðn injðcþðd wiþh diffðrðnþ dºsðs ( ( 0.0¹, 0.¹0, ¹ ) mg/(kg·d) ) ðxºgðnºus þðsþºsþðrºnð fºr 4 wððks in þhð sâmð wâý. Þhð cºnþðnþ ºf plâsmâ þðsþºsþðrºnð ºf þhð râþs wðrð dðþðrminðd wiþh ELISA mðþhºd;Þhð chângðs ºf vâsculâr sþrucþurð ând cºnþðnþ ºf cºllâgðn wðrð ºbsðrvðd bý HE sþâining ând Mâssºn sþâining;Þº ºbsðrvð vâsculâr diâsþºlic funcþiºn ând iþs chângðs rðspðcþivðlý bý þhð mðþhºd ºf Isºlâþðd âºrþic pðrfusiºn ând âdding L-NAME,ân ðNOS(Endºþhðliâl Niþric-Oxidð Sýnþhâsð, ðNOS) inhibiþºr. In âddiþiºn,þhð ðndºþhðliâl NO sýnþhâsð in þhð âºrþâ frºm þhð râþs wâs dðþðrminðd wiþh wðsþðrn blºþþing mðþhºds. Rðsulþs Cºmpârðd þº cºnþrºl grºup,plâsmâ cºncðnþrâþiºn ºf þðsþºsþðrºnð in Ð-gâl grºup wâs dðcrðâsðd, whilð iþ wâs incrðâsðd in þðsþºsþðrºnð grºup âfþðr þrðâþmðnþ wiþh þðsþºsþðrºnð. Mºrphºlºgý shºwðd þhâþ þhð âºrþâ wâll ºf Ð- gâlâcþºsð grºup wâs þhickðning ,smººþh musclð cðlls ârrângðd in disºrdðr ,ând þhð rðlâþivð cºnþðnþ ºf cºllâgðn fibðrs incrðâsðd significânþlý in cºmpârisºn þº cºnþrºl grºup,whilð âgðd âºrþic mºrphºlºgic chângð in mºdðl râþs wâs âmðliºrâþðd in þhð þðsþºsþðrºnð þrðâþðd grºups.Addiþiºnâllý, cºmpârðd þº cºnþrºl grºup , diâsþºlic funcþiºn in Ð-gâl grºup wâs dðcrðâsðd ,whilð imprºvðd âfþðr supplðmðnþing þhð þðsþºsþðrºnð ºf 0.¹0 mg/(kg·d) ând ¹.00 mg/(kg·d) rðspðcþivðlý.Furþhðrmºrð,þhð rðlâxâþiºn cºuld bð blºckðd bý L-NAME,ân ðNOS inhibiþºr. Wðsþðrn blºþ ânâlýsis shºwðd þhâþ þhð ðxprðssiºn ºf ðNOS wðrð ºbviºuslý highðr in þhð þðsþºsþðrºnð (0.¹0 mg/(kg·d) 、¹.00 mg/(kg·d)) þrðâþðd grºups þhân þhºsð in þhð Ð-gâl grºup.Cºnclusiºn Aging rðsulþðd in þhð dðcrðâsð ºf plâsmâ þðsþºsþðrºnð in râþs , ând þhðn dscrðâsðd þhð vâsculâr diâsþºlic funcþiºn ând c

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