青春期前己烯雌酚暴露对大鼠性成熟后生精细胞凋亡的影响及其机制初探

目的:研究青春期前己烯雌酚(d iethylstilbestrol,DES)暴露对SD大鼠性成熟后睾丸生精细胞凋亡的影响并初步探讨其机制。方法:30只21日龄雄性SD大鼠,随机分为DES 0.01、0.1、1.0、10.0μg/(kg.d)4个实验组和1个对照组(编码为ADa、ADb、AD c、ADd和AC组,每组6只)。于青春期前[出生后第22 d(postnatal day 22,PND22)至35 d(PND35)],实验组每日皮下注射相应剂量的DES,对照组仅注射溶媒。于大鼠性成熟后(PND 64)处死各组大鼠切取双侧睾丸,采用TUNEL法检测大鼠睾丸生精细胞凋亡,用免疫组化方法检测凋亡相关蛋白Bc l-2和Bax在生精细胞中的表达。结果:与对照组相比,ADa组大鼠性成熟后生精细胞凋亡无明显变化,ADb、AD c和ADd 3组生精细胞凋亡增加,且随DES暴露剂量增加而有增加趋势。AC、ADa组生精细胞Bax相对弱表达而Bc l-2强表达,伴随DES暴露剂量增加,Bax表达逐渐增强而Bc l-2表达逐渐减弱,ADd组Bax强表达而Bc l-2弱表达。结论:青春期前较大剂量DES暴露可使大鼠性成熟后睾丸生精细胞凋亡增加,且随DES暴露剂量增加而有加强趋势。凋亡相关蛋白Bax和Bc l-2参与青春期前DES暴露所致的生精细胞凋亡过程。     

单侧隐睾大鼠对侧睾丸的损害与Bcl-2和Bax基因表达

目的:探讨单侧隐睾大鼠对侧睾丸生精细胞凋亡与Bcl-2/Bax基因表达的关系。方法:20只健康SD雄性大鼠(22日龄)随机分成隐睾组和对照组,每组10只。通过手术建立单侧隐睾动物模型。术后90 d取对侧睾丸,采用原位缺口末端标记(TUNEL)法检测生精细胞凋亡,免疫组化SP法检测Bcl-2/Bax基因表达。结果:与对照组相比,隐睾组对侧睾丸生精细胞凋亡显著增多(P<0.01),重量显著减轻(P<0.01),Bax表达显著升高(P<0.01),Bcl-2表达显著降低(P<0.01)。凋亡细胞主要是初级精母细胞和圆形精子细胞。结论:单侧隐睾大鼠对侧睾丸的生精细胞凋亡增多与Bcl-2基因表达降低、Bax基因表达升高密切相关。细胞内Bc l-2/Bax比值是影响生精细胞凋亡的重要因素之一。     

腹股沟区皮下埋藏睾丸对生精细胞凋亡及Bcl-2/Bax蛋白表达的影响

目的:通过观察腹股沟区皮下埋藏睾丸生精细胞的凋亡及Bcl-2/Bax蛋白表达,探讨二者的关系。方法:以健康育龄期36只雄性新西兰大白兔为实验动物,随机分成实验组18只、对照组18只。实验组动物将双侧睾丸分别移位埋藏至双侧腹股沟区皮下,以制备睾丸埋藏修复阴囊皮肤缺损模型;对照组未作处理。动物模型建立后第8周末,每组随机取6只大白兔测量睾丸表面温度后进行睾丸活检。睾丸组织行原位末端标记(TUNEL)法检测生精细胞凋亡、免疫组化法结合图像分析仪检测睾丸生精细胞Bcl-2、Bax蛋白的表达。结果:对照组的睾丸表面温度为(36.15±0.64)℃,实验组为(38.02±0.36)℃,两组比较差异有统计学意义(P<0.05)。模型建立后第8周末实验组睾丸生精小管中生精细胞的凋亡指数(AI)为(89.69士3.76)%,对照组为(7.73±4.95)%,两者比较有显著差异(P<0.05)。实验组Bax表达显著升高(P<0.05),Bcl-2表达显著降低(P<0.05),凋亡细胞主要为初级精母细胞和圆形精子细胞。结论:腹股沟区皮下埋藏睾丸局部温度升高诱导睾丸的生精细胞凋亡增加,生精细胞凋亡增加与Bcl-2蛋白表达降低、Bax蛋白表达升高密切相关。Bcl-2/Bax的改变是高温引起生精细胞凋亡的机制之一。     

荧光定量聚合酶链反应检测去颌下腺大鼠睾丸Bc1 2和Bax mRNA的改变

目的 观察切除颌下腺对大鼠睾丸Bax和Bc1 2 mRNA表达的影响.方法 切除大鼠颌下腺,分别于术后14、28和42 d处死大鼠,提取睾丸总RNA,反转录,设计特异性引物和Taqman探针,荧光定量聚合酶链反应(PCR)检测Bax和Bc1 2 mRNA的改变.结果 随着颌下腺切除时间的延长,实验组大鼠睾丸Bax和Bc1 2 mRNA的比值显著升高,与对照组比较,有显著性差异(P<0.01).结论 颌下腺切除大鼠睾丸Bax和Bc1 2 mRNA比值明显升高,提示颌下腺切除所致的大鼠睾丸生精细胞的凋亡可能是由Bax和Be1 2介导的线粒体途径进行,但Fas/FasL是否参与该凋亡过程还有待进一步研究.     

低氧对大鼠睾丸生殖细胞凋亡的影响

目的:研究低氧对大鼠睾丸生殖细胞凋亡和Bax、Bcl-2表达的影响。方法:雄性成年Wistar大鼠随机分为4组:常氧对照组、低氧5 d组、低氧15 d组和低氧30 d组(各组n=6)。常氧对照组在平原喂养;低氧5 d组、15 d组和30 d组分别在低压舱内模拟5 000 m高原喂养5、15、30 d。采用流式细胞术和TUNEL法检测低氧对睾丸生殖细胞凋亡的影响。运用Western印迹技术检测低氧对大鼠睾丸内凋亡相关蛋白Bax、Bcl-2表达的影响。结果:低氧5 d组、15 d组和30 d组睾丸内发生生殖细胞凋亡的生精小管数量[每100个生精小管中,含有凋亡生殖细胞的生精小管数分别为(20.50±5.07)、(21.25±7.85)、(14.00±2.45)个]均非常显著地高于常氧对照组[(6.00±2.16)个,P<0.01]。凋亡的生殖细胞以精原和精母细胞为主。低氧15 d组睾丸组织亚单倍体细胞百分率[(2.18±0.82)%]显著高于常氧对照组[(1.30±0.33)%,P<0.05],低氧30 d组[(3.08±0.93)%]极显著高于常氧对照组(P<0.01)。低氧30 d组睾丸组织Bax表达显著高于常氧对照组(P<0.05),其灰度值分别为17.34±4.54和10.50±2.82。低氧30 d组睾丸组织Bax/Bcl-2比值显著高于常氧对照组(P<0.01),比值分别为0.40±0.10和0.27±0.04。结论:低氧诱导大鼠睾丸生殖细胞凋亡增多,慢性低氧引起的睾丸生殖细胞凋亡增多与Bax表达增加有关。     

单侧睾丸扭转后生精细胞凋亡的分子途径

目的:研究大鼠单侧睾丸扭转复位后生精细胞凋亡的分子机制。方法:雄性SD大鼠16只,随机分为对照组和扭转组,每组8只。建立睾丸扭转动物模型(720°2h),术后24h留取手术侧睾丸。应用流式细胞术检测生精细胞凋亡和各级生精细胞计数,应用RT-PCR技术对Fas/FasL mRNA和Bax mRNA进行半定量分析,Western印迹技术检测细胞色素C含量。结果:两组间生精细胞凋亡及各类生精细胞计数均有显著性差异(P<0.01)。扭转组FCM直方图呈现高大凋亡峰,单倍体和四倍体细胞群计数下降,Fas/FasL mRNA和Bax mRNA表达上调,同时细胞质中细胞色素C含量亦明显升高,与对照组相比其差异均有显著性(P均<0.01)。结论:睾丸扭转复位后生精细胞凋亡存在着外源性和内源性两条基本途径。凋亡相关分子Fas/FasL表达上调和Bax介导的细胞色素C释放可能是睾丸扭转后生精细胞凋亡的重要环节。     

二甲双胍对营养性肥胖大鼠附睾精子质量和睾丸抗氧化能力的影响

目的:观察二甲双胍对高脂饮食诱导的肥胖大鼠附睾精子质量和睾丸抗氧化能力的影响。方法:雄性SD大鼠分为正常对照组和造模组,造模组以高脂饲料喂养8周后,取24只肥胖大鼠随机分为模型对照组、二甲双胍组和普通饲料组,除模型对照组继续高脂饲料喂养外,其余3组普通饲料喂养。12周末,所有大鼠均禁食12 h后处死,检测Lee's指数、睾丸和附睾脏器指数,附睾精子浓度、精子活动率和a+b级精子百分率,睾丸组织匀浆中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)含量。结果:Lee's指数模型对照组与其他3组比较显著升高(P<0.01),Lee's指数正常对照组较二甲双胍组升高(P<0.05)。睾丸、附睾、脏器指数模型对照组较其他3组显著降低(P<0.01)。精子浓度、精子活动率和a+b级精子百分率模型对照组与其他3组比较显著降低(P<0.05或P<0.01),正常对照组较二甲双胍组和普通饲料组精子浓度升高(P<0.05)。SOD含量(U/mg prot)模型对照组(90.92±4.06)较正常对照组(101.69±8.49)与二甲双胍组(102.04±10.67)降低(P<0.05)。GSH-Px含量(U)正常对照组(28.32±2.28)较模型对照组(23.49±1.08,P<0.01)、二甲双胍组(25.73±2.14,P<0.05)和普通饲料组(25.77±2.19,P<0.05)升高,模型对照组较二甲双胍组降低(P<0.05)。MDA含量(nmol/mg prot)模型对照组(2.68±0.76)较正常对照组(1.84±0.31,P<0.01)、二甲双胍组(1.88±0.33,P<0.01)和普通饲料组(2.14±0.35,P<0.05)升高。结论:二甲双胍治疗和饮食改善均可提高营养性肥胖大鼠精子质量,改善睾丸组织抗氧化能力。     

荧光定量聚合酶链反应检测去颌下腺大鼠睾丸Bcl 2和Bax mRNA的改变

目的观察切除颌下腺对大鼠睾丸Bax和Bcl 2 mRNA表达的影响。方法切除大鼠颌下腺,分别于术后14、28和42 d处死大鼠,提取睾丸总RNA,反转录,设计特异性引物和Taqman探针,荧光定量聚合酶链反应(PCR)检测Bax和Bcl 2 mRNA的改变。结果随着颌下腺切除时间的延长,实验组大鼠睾丸Bax和Bcl 2 mRNA的比值显著升高,与对照组比较,有显著性差异(P<0.01)。结论颌下腺切除大鼠睾丸Bax和Bcl 2 mRNA比值明显升高,提示颌下腺切除所致的大鼠睾丸生精细胞的凋亡可能是由Bax和Bcl 2介导的线粒体途径进行,但Fas/FasL是否参与该凋亡过程还有待进一步研究。     

营养性肥胖对青春期雄性大鼠睾丸发育过程的影响

目的:探讨以高脂饲料配方建立的营养性肥胖大鼠模型对青春期雄性大鼠睾丸发育过程的影响。方法:21日龄雄性清洁级SD大鼠80只,断奶适应性饲养3 d后,随机分为对照组(n=32)和实验组(n=48)。以高脂饲料建立营养性肥胖动物模型。观察喂养后第3、4、5、6周末(即鼠龄为6、7、8、9周)大鼠体重、Lee's指数、睾丸重量、附睾重量的变化;全自动生化分析仪检测外周血甘油三酯(TG)和总胆固醇(TC);全自动微粒子化学发光免疫分析系统检测血清T、E2;HE染色观察睾丸发育的形态学改变。结果:高脂喂养的实验组大鼠在第3周末平均体重已明显增加(P<0.05),至第6周末,实验组大鼠较对照组超重达26.6%(P<0.01),Lee's指数也明显大于对照组(P<0.01);实验组大鼠第5、6周末的睾丸系数下降明显(P<0.05);实验组每周龄大鼠血清TG,TC水平均比对照组明显升高;实验组每周龄大鼠的T水平均明显低于对照组(P<0.05),E2水平在第3、4、5周虽低于对照组,而在第6周则呈现明显增加趋势,且显著高于对照组(P<0.01);光镜下可见实验组大鼠睾丸生精上皮细胞排列紊乱,细胞层次减少,成熟的精子数量较少。结论:高脂、高能量饮食可诱发青春期雄性大鼠营养性肥胖,随着肥胖程度的逐渐加重,可造成睾丸发育不全、睾丸生殖内分泌功能障碍。     

多菌灵对大鼠睾丸发育和生精功能影响的研究

目的:探讨多菌灵对雄性大鼠睾丸发育和生精功能的影响及其作用机制。方法:40只清洁级未成年Wistar雄性大鼠随机分为4组(对照组,低、中、高剂量组,每组10只),低、中、高剂量组经口灌胃不同浓度的多菌灵溶液(分别为20、100、200mg/kg体重),对照组给予吐温80溶液,1次/d,连续80d。染毒结束后,立即取睾丸和附睾,观察其形态。测定各组大鼠体重及右侧睾丸和附睾重量;取左侧附睾尾测定精子活率和精子数量;采用HE染色法、原位末端标记法(TUNEL)及免疫组化SABC法观察大鼠睾丸组织的病理学变化、细胞凋亡和Bcl-2/Bax表达情况。结果:中、高剂量组大鼠睾丸和附睾均明显萎缩、右侧睾丸和附睾重量减轻,左侧附睾尾精子活率和精子数量均低于对照组(P<0.01);中、高剂量组睾丸组织病理学检查可见明显异常;随多菌灵染毒浓度的增加,各剂量组生精细胞凋亡率逐渐升高,Bcl-2表达下降,Bax表达升高,与对照组比较差异有统计学意义(P<0.05,P<0.01)。结论:多菌灵可影响雄性大鼠的睾丸发育和生精功能,可能与下调Bcl-2和上调Bax致细胞凋亡增加有关。     

An animal model to study lower urinary tract symptoms and erectile dysfunction: the hyperlipidaemic rat

OBJECTIVE: To present evidence that rats fed a high-fat diet could serve as a useful animal model to study both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED), as recent epidemiological studies have shown a strong association between LUTS and ED but the physiological basis behind this relationship is unknown. MATERIALS AND METHODS: In all, 24 male Sprague-Dawley rats were divided into two groups: nine controls were fed a 'normal' diet and 15 were fed a high-fat diet (hyperlipidaemic rats). After 6 months all the rats had bladder and erectile functions evaluated using awake cystometry and cavernosal nerve electrostimulation, respectively. After the functional studies were completed, the penis, prostate and bladder were collected for immunohistochemical analysis. RESULTS: The hyperlipidaemic rats had significantly higher serum cholesterol and low-density lipoprotein than the controls (P < 0.05). The hyperlipidaemic rats also had significantly worse erectile function (P = 0.004) and developed more bladder overactivity (P = 0.004) than the controls. In the hyperlipidaemic rats there was significant muscle hypertrophy in the peri-urethral lobe of the prostate (P < 0.001) and in the bladder (P < 0.05). There was also greater P2X(1) (purinoceptor) staining as well as other molecular changes in the bladder of the hyperlipidaemic rats. CONCLUSIONS: In this hyperlipidaemic rat model three abnormalities were consistently detected: prostatic enlargement, bladder overactivity, and ED. This rat model could be a useful research tool for understanding the common causes of LUTS and ED, as well as facilitating the development of preventive measures and better therapies to treat both conditions.     

Low-level laser therapy (LLLT) combined with swimming training improved the lipid profile in rats fed with high-fat diet

Obesity and associated dyslipidemia is the fastest growing health problem throughout the world. The combination of exercise and low-level laser therapy (LLLT) could be a new approach to the treatment of obesity and associated disease. In this work, the effects of LLLT associated with exercises on the lipid metabolism in regular and high-fat diet rats were verified. We used 64 rats divided in eight groups with eight rats each, designed: SC, sedentary chow diet; SCL, sedentary chow diet laser, TC, trained chow diet; TCL, trained chow diet laser; SH, sedentary high-fat diet; SHL, sedentary high-fat diet laser; TH, trained high-fat diet; and THL, trained high-fat diet laser. The exercise used was swimming during 8 weeks/90 min daily and LLLT (GA-Al-As, 830 nm) dose of 4.7 J/point and total energy 9.4 J per animal, applied to both gastrocnemius muscles after exercise. We analyzed biochemical parameters, percentage of fat, hepatic and muscular glycogen and relative mass of tissue, and weight percentage gain. The statistical test used was ANOVA, with post hoc Tukey–Kramer for multiple analysis between groups, and the significant level was p?<?0.001, p?<?0.01, and p?<?0.05. LLLT decreased the total cholesterol (p?<?0.05), triglycerides (p?<?0.01), low-density lipoprotein cholesterol (p?<?0.05), and relative mass of fat tissue (p?<?0.05), suggesting increased metabolic activity and altered lipid pathways. The combination of exercise and LLLT increased the benefits of exercise alone. However, LLLT without exercise tended to increase body weight and fat content. LLLT may be a valuable addition to a regimen of diet and exercise for weight reduction and dyslipidemic control.     

Paradoxical increase in nitric oxide synthase activity in hypercholesterolaemic rats with impaired renal function and decreased activity of nitric oxide.

BACKGROUND: We have shown that acute exposure of oxidized low-density lipoprotein (OX-LDL) induces vasoconstriction in renal vessels and reduces glomerular filtration rate (GFR) in an isolated perfused rat kidney model by decreasing the activity of nitric oxide (NO). L-arginine has a protective role against OX-LDl-induced vasoconstriction. Micropuncture studies have demonstrated that short-term diet-induced hypercholesterolaemia is associated with decreased GFR and renal blood flow and increased glomerular capillary pressure. This may be mediated by decreased activity of NO. METHODS: Rats were made hypercholesterolaemic by supplementing the standard chow with 4% cholesterol and 1% sodium cholate. A group of rats on hypercholesterolaemic diet also received L-arginine in the drinking water. After 4 and 6 weeks, blood samples and 24-h urine samples were collected for the measurement of biochemical parameters. After 6 weeks, all rats were subjected to isolated perfusion of kidneys at a constant pressure of 100 mmHg. During isolated perfusion, the unused contralateral kidney was taken for morphological studies and for assessing the activity of nitric oxide synthase enzyme by beta-NADPH diaphorase histochemistry. RESULTS: Rats fed a high-cholesterol diet had LDL levels 3-6 times greater than the rats fed standard chow. Rats that received L-arginine in the drinking water had serum L-arginine levels 5-6 times greater than control rats. At 6 weeks, creatinine clearance was significantly lower in the rats on the high-cholesterol diet compared to the rats on standard chow and rats on high-cholesterol diet plus L-arginine. Twenty-four-hour urinary total nitrate and nitrite excretion in the hypercholesterolaemic rats was 1.5-2 times greater than that of control rats. Twenty-four-hour urinary cGMP excretion was significantly lower in the rats on a high-cholesterol diet, but in the rats on high-cholesterol diet and L-arginine, 24-h urinary cGMP excretion was not significantly different from that of control rats. During isolated perfusion of kidneys, renal perfusate flow was found to be significantly reduced in the kidneys taken from the rats on a high-fat diet compared to controls. L-arginine supplementation in the drinking water almost completely reversed the effect of a high-fat diet. Inulin clearance was also significantly reduced in kidneys on a high-fat diet in contrast to controls but not in kidneys on high fat-diet and L-arginine. Basal cGMP excretion in urine was significantly lower in the kidneys taken from the rats on a high-fat diet compared to controls. L-arginine supplementation restored the basal cGMP excretion in these kidneys. NO synthase (NOS) enzyme activity as assessed by NADPH diaphorase activity showed that kidney sections taken from the rats on a high-fat diet showed more intense staining, indicating increased activity compared to the kidney sections taken from the rats on a normal diet. CONCLUSION: Though activity of NO is diminished in hypercholesterolaemic rats with impaired renal function, there is a paradoxical increase in NO production and NOS activity. L-arginine reverses the effects of a high-fat diet.     

洛伐他汀对肾小球硬化大鼠基质金属蛋白酶抑制因子-1表达的影响

目的:探讨洛伐他汀对阿霉素肾病肾小球硬化大鼠基质金属蛋白酶抑制因子-1(TIMP-1)的影响.方法:24只雄性Wistar大鼠,随机分为正常对照组(A组),模型组(B组),治疗组(C组).B组、C组按5 mg/kg于尾静脉注射阿霉素,A组行尾静脉注射等量生理盐水;同时,A组给予普通饲料喂养,B组、C组给予高胆固醇饲料,C组予灌胃洛伐他汀4 mg·kg-1·d-1,A、B两组大鼠仅灌以2 ml蒸馏水.12周后处死大鼠,切取右肾用于肾脏病理分析,免疫组化法检测肾组织TIMP-1的表达.结果:治疗组血胆固醇、甘油三酯、低密度脂蛋白、尿蛋白、肾脏病理积分及泡沫细胞明显低于高脂组,肾脏免疫组化显示治疗组TIMP-1表达明显减少.结论:洛伐他汀可减轻肾小球硬化,除与其降血脂作用有关外,可能与减少TIMP-1在肾脏中的表达有关.     

The Effects of Splenectomy and Splenic Autotransplantation on Plasma Lipid Levels

Purpose: Atherosclerosis observations after splenectomy for trauma and hypersplenism suggests a possible role for the spleen in lipid metabolism. The authors examined the effects of splenectomy on serum lipids in rats and also cholesterol-fed rats with experimental atherosclerosis. Methods: This study was designed on rats. The rats were divided into five groups: splenectomy, normal diet (SP-N, n: 8), splenectomy, cholesterol-fed groups (SP-C, n: 8), splenic autotransplantation after splenectomy, normal diet (SA-N, n: 8), splenic autotransplantation after splenectomy, cholesterol-fed groups (SA-C, n: 8) and sham groups (n: 8). Total triglyceride, total cholesterol, HDL (high-density lipoprotein), LDL (low-density lipoprotein), and VLDL (very low-density lipoprotein) levels were determined in 40 rats. The rats were classified into five groups based on the surgical procedures. The spleens were removed and then the rats were fed a normal diet in Group SP-N (n = 8). The spleens were removed and then the rats were fed a diet containing 1% cholesterol in Group SP-C (n = 8). Splenectomy and splenic autotransplantations were performed and then the rats were fed a normal diet in Group SA-N (n = 8). Splenectomy and splenic autotransplantations were performed and then the rats were fed a diet containing 1% cholesterol in Group SA-C (n = 8). The rats were sham-operated in the control group (Group S, n = 8). An active splenic function was shown in rats that underwent splenic autotransplantation in both groups by using Technicium 99 m sulphurcolloide sintiscan on day 30. Blood lipid levels were repeated 6 months later. Results: There was no difference between pre- and postoperative lipid levels in the sham group and SA-N group (p >.05). All lipid levels including HDL were increased significantly in SP-C group (p <.05). Also VLDL and total tryglyceride levels were increased significantly in SP-N and SA-C groups (p <.05). Conclusions: This study showed that the spleen might have an important effect on lipid metabolism and splenic autotransplantation may be protective in conditions with increased lipid levels.     

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

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。     

Effect of hyperlipidemia on femoral biomechanics and morphology in low-density lipoprotein receptor gene knockout mice

The objective of this study was to evaluate the effect of hyperlipidemia on the biomechanical and morphological properties of the femur of low-density lipoprotein receptor gene knockout mice (LDLr-/-) mice. Ten wild-type mice (C57BL6) and 10 LDLr-/- mice generated on a C57BL6 background were used. Male 3-month-old animals were divided into four groups (n = 5): group W (wild type) and group L (LDLr-/-) receiving low-fat commercial ration, and group WH (wild type) and group LH (LDLr-/-) receiving a high-fat diet. After 60 days, blood samples were collected for laboratory analysis of calcium, triglycerides, and cholesterol. The femur was excised for mechanical testing and morphometric analysis. LDLr-/- mice receiving the high-fat diet presented more marked alterations in the mechanical and morphological properties of femoral cortical and trabecular bone. Changes in the plasma levels of calcium, triglycerides, cholesterol, and fractions were also more pronounced in this group. The present results demonstrate that hyperlipidemia causes alterations in the structure and mechanical properties of the femur of LDLr-/- mice. These effects were more pronounced when associated with a high-fat diet.     

Synergistic action of inflammation and lipid dysmetabolism on kidney damage in rats

In kidney disease, inflammation and lipid dysmetabolism are often associated together, however, the effect and mechanism of inflammatory mediators and lipid dysmetabolism on kidney damage is still unclear. In this study, Wistar rats were randomized into four groups: normal diet?+?saline (Group N), high-fat diet (HF)+?saline (Group HF), normal diet?+?adriamycin (Group ADR), HF?+?adriamycin (Group ADR?+?HF). After 10?weeks of feeding, rats in each group were randomly sacrificed. We found that the protein content of urine in ADR and ADR?+?HF groups were significantly higher than that of group N and HF while the serum levels of total protein and albumin in the ADR and ADR?+?HF groups decreased correspondingly. The serum levels of triglyceride, total cholesterol and low-density lipoprotein in the HF, ADR and ADR?+?HF groups increased. In the treatment groups, mesangial proliferation, matrix accumulation, tubular vacuolization, inflammatory cell infiltration and fat deposition were detected. These pathological changes were the most serious in the ADR?+?HF group. The expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) were increased in each treatment group, especially in the ADR?+?HF group. Our results suggested that the inflammatory factors and abnormal lipid levels can activate the inflammatory response in kidney of the Wistar rats, and lead to a series of pathological changes in renal tissue, and inflammatory factors and lipid dysmetabolism can aggravate damage in the kidney.     

HMG-CoA reductase, cholesterol 7alpha-hydroxylase, LDL receptor, SR-B1, and ACAT in diet-induced syndrome X

BACKGROUND: Long-term consumption of Western diets can lead to acquired syndrome X, which presents with obesity, insulin resistance, hypertension, hyperlipidemia, and risk of atherosclerotic cardiovascular disease. While plasma lipid abnormalities in syndrome X have been well characterized, their molecular basis remains unclear. This study explored potential mechanisms of hypercholesterolemia in diet-induced syndrome X. METHODS: Female Fischer rats were fed a high-fat, refined-carbohydrate (sucrose) diet (HFS) or standard rat chow (low-fat, complex carbohydrate, LFCC) for 20 months. Plasma lipids and hepatic tissue mRNA, protein, and/or activities of the key enzymes and receptors involved in cholesterol metabolism were determined. RESULTS: The HFS group exhibited hypertension, hyperlipidemia, insulin resistance, obesity, significant down-regulation of hepatic cholesterol 7alpha-hydroxylase (the rate-limiting step in cholesterol catabolism) and low-density lipoprotein (LDL) receptor (LDL-R, the primary pathway of LDL clearance). In contrast, hepatic tissue acyl-coenzyme A:cholesterol acyltransferase (ACAT-2, the primary enzyme involved in intracellular esterification of cholesterol) and scavenger-receptor class B, type 1 (SR-B1 or HDL receptor) were up-regulated. While 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA expression was increased, its protein abundance and activity were unchanged, and HMG-CoA reductase-to-cholesterol 7alpha-hydroxylase ratio was increased in HFS-fed animals. CONCLUSION: Hypercholesterolemia in diet-induced syndrome X is associated with depressed cholesterol 7alpha-hydroxylase, diminished LDL-R, elevated ACAT, and increased HMG-CoA reductase-to-cholesterol 7alpha-hydroxylase ratio. These findings point to impaired hepatic catabolism and uptake of cholesterol and inappropriate cholesterol production capacity as the underlying causes of hypercholesterolemia in rats with diet-induced syndrome X.