高脂饮食上调大鼠慢性炎症水平导致勃起功能障碍发生风险增高

High-fat diet up-regulates the chronic inflammation then increases the risk of erectile dysfunction in rats

目的探讨高脂饮食(high-fat diet,HFD)对勃起功能的影响。方法将20只10月龄雄性SD大鼠随机分成两组:对照组(n=10,喂食常规饲料)和模型组(n=10,喂食高脂饲料)。4个月后,检测其体重、空腹血糖和血脂水平等指标,同时用最大海绵体内压(max intracavernous pressure,Max ICP)和平均动脉压(mean arterial pressure,MAP)的比值评价其勃起功能,探讨HFD对勃起功能的影响。而后采用苏木精-伊红(H&E)染色观察肝脏和阴茎组织的形态学变化、Masson's三色染色观察海绵体平滑肌纤维化程度;免疫组化检测海绵体组织中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白介素-6(interleukin-6,IL-6)表达水平;Western blot检测海绵体组织中磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)、丝氨酸/苏氨酸激酶(protein kinase B,AKT)、核因子κB(nuclear factor-kappa B,NF-κB)、TNF-α和IL-6等蛋白的表达情况,研究HFD激活炎症导致勃起功能改变的可能机制。结果与对照组比较,模型组的体重增量、总胆固醇(total cholesterol,TCH)、甘油三酯(triglyceride,TG)和低密度脂蛋白(low density lipoprotein,LDL)等水平均明显升高(P<0.05);Max ICP/MAP值降低(P<0.001);肝脏组织中出现大量脂滴空泡;海绵体平滑肌细胞(cavernosum smooth muscle cells,CSMCs)排布欠规则,肌纤维间隙增宽,肌纤维含量明显减少,胶原纤维含量明显增多;内皮细胞(endothelial cells,ECs)萎缩,连续性中断;同时其海绵体组织中PI3K、AKT、NF-κB、TNF-α和IL-6等的表达水平明显升高(P<0.05)。结论HFD可引起大鼠海绵体组织炎性水平升高,导致CSMCs和ECs形态异常,增加其患勃起功能障碍(erectile dysfunction,ED)的风险。

Objective To investigate the effect of high-fat diet(HFD)on erectile function.Methods Twenty10-month-old male SD rats were randomly divided into the control group(norm diet n=10)and the model group(high-fat diet n=10).After 4 months of feeding,the levels of body weight,blood glucose and blood lipid in rats were measured.Erectile function was measured by max intracavernous pressure(Max ICP)/mean arterial pressure(MAP).Hematoxylin-eosin(H&E)staining was used to observe the pathological changes of liver and corpus cavernosum tissues.Masson’s Trichrome staining was used to observe the degree of cavernous fibrosis.The expressions of TNF-αand IL-6 proteins in corpus cavernosum were detected by immunohistochemistry(IHC).The expressions of phosphatidylinositol 3-kinase(PI3 K),protein kinase B(AKT),nuclear factor-kappa B(NF-κB),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)proteins in corpus cavernosum were detected by Western blot.Results Compared with those of the control group,the levels of body weight,serum total cholesterol(TCH),triglyceride(TG)and low density lipoprotein(LDL)were significantly increased in HFD rats(P<0.05)and their Max ICP/MAP was significantly decreased(P<0.001).H&E staining showed that liver tissues were exhibited steatosis,continuous interruption of cavernosum smooth muscle cells(CSMCs)and endothelial cells(ECs);Masson’s Trichrome staining indicated that the smooth muscle were decreased,cavernous fibrosis was increased.IHC analysis demonstrated that the expression levels of TNF-αand IL-6 in corpus cavernosum were significantly increased(P<0.01).Western blot suggested that the expression levels of PI3 K,AKT,NF-κB,TNF-αand IL-6 in corpus cavernosum were significantly increased(P<0.05).Conclusion HFD may elevate levels of inflammatory factors,to cause CSMCs and ECs dysfunction,in turn increase the risk of erectile dysfunction(ED)in rats.