低氧诱导因子1α在高脂饮食诱导肥胖小鼠前列腺组织中的表达

Expression of HIF-1α in the prostatic tissue of mice with high-fat diet-induced obesity

目的:观察低氧诱导因子1α(HIF-1α)在高脂饮食诱导C57BL/6J小鼠前列腺组织中的表达,以探讨缺氧对肥胖小鼠前列腺增生的作用。方法:将20只小鼠随机分为对照组(普通饮食)和高脂饮食组,各10只。高脂饮食组高脂饮食干预17周,测量小鼠体重,解剖取材测量前列腺重量,排水法测量前列腺体积,ELISA法检测血清甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、游离脂肪酸(FFA)的含量;HE染色观察前列腺组织形态并测量其腺腔面积,免疫组化检测前列腺组织HIF-1α的表达。结果:①高脂饮食组小鼠体重为(42.55±3.01) g、前列腺重量(0.13±0.03)g、前列腺体积(0.14±0.03)ml、TG(179.29±65.19) mmol/L、LDL(66.88±1.93)g/L,均显著高于对照组[(28.94±2.17) g、(0.05±0.03) g、(0.05±0.02) ml、(115.77±25.25) mmol/L,(44.16±7.24)g/L](P<0.01或<0.05)。②组织病理学结果显示,对照组小鼠前列腺上皮表现为单层立方上皮和单层柱状上皮,高脂饮食组则主要表现为不规则上皮结构;高脂饮食组小鼠前列腺腺腔面积显著大于对照组[(18 453±7 311)μm^2vs(12 390±8 587)μm^2,P<0.01]。③高脂饮食组前列腺组织HIF-1α积分光密度值明显高于对照组[(9.1±6.9)×10^6vs(2.0±3.6)×10^6,P<0.01]。④相关性分析表明,前列腺体积与体脂肪重量(r=0.887,P<0.01)、TG(r=0. 520,P=0.047)、LDL(r=0.772,P=0.010)呈正相关。结论:肥胖小鼠脂代谢异常使前列腺组织出现局部低氧从而引发BPH。

Objective: To investigate the expression of hypoxia-inducible factor-1α(HIF-1α) in the prostatic tissue of mice with high-fat diet-induced obesity and to explore the effect of hypoxia on BPH in obese male mice. Methods: We randomly divided 20 C57 BL/6 J male mice into two groups of equal number and fed them on a high-fat diet(HFD group) or a normal diet(control group) for 17 weeks. Then, we measured the body weight, prostate weight, prostate volume and levels of serum triglycerides(TG), high-density lipoprotein(HDL), low-density lipoprotein(LDL) and free fatty acids(FFA) by ELISA, observed the morphology of the prostate by HE staining, calculated the area of the prostatic glandular cavity, and determined the expression of HIF-1α in the prostatic tissue by immunohistochemistry. Results: Compared with the controls, the mice fed on the HFD showed significant increases in the body weight([28.94 ± 2.17] vs [42.55 ± 3.01] g, P < 0.01), prostate weight([0.05 ± 0.03] vs [0.13 ± 0.03] g, P < 0.01), prostate volume([0.05 ± 0.02] vs [0.14 ± 0.03] ml, P < 0.01), and the levels of TG([115.77 ± 25.25] vs [179.29 ± 65.19] mmol/L, P = 0.022), HDL([67.14 ± 3.10] vs [72.84 ± 1.91] g/L, P < 0.01) and LDL([44.16 ± 7.24] vs [66.88 ± 1.93] g/L, P < 0.01) at 17 weeks. Histopathological examination exhibited single-layer cuboidal or columnar prostatic epithelium in the controls but an irregular epithelial structure and a larger area of the prostatic glandular cavity in the HFD group([12 390 ± 8 587] vs [18 453 ± 7 311]μm^2, P < 0.01). The integrated optical density(IOD) of HIF-1α was markedly higher in the HFD group([9.1 ± 6.9]× 10^6) than in the control([2.0 ± 3.6]×10^6)(P < 0.01). The prostate volume was positively correlated with the body fat weight(r = 0.887, P = 0.01), TG(r = 0.520, P = 0.047) and LDL(r = 0.772, P = 0.010). Conclusion: Abnormal lipid metabolism may induce local hypoxia in the prostate tissue and lead to BPH in obese mice.