代谢综合征基础与临床系列研究——GRGDSP/7E3对动脉粥样硬化内皮细胞MMPs的mRNA表达的影响

目的了解GRGDSP/7E3对基质金属蛋白酶（MMP-2,MMP-9）mRNA表达的影响。方法体外培养人脐静脉内皮细胞,分别用酶谱法和逆转录聚合酶链式反应（RT-PCR）检测MMP-2,MMP-9活性和mRNA表达。待细胞融合成单层后,分别加入无血清培养基、静息期血小板、活化后血小板及interleukin-1β（IL-1β）,共同培养60min后,洗去血小板,内皮细胞继续培养6h。上清液及细胞分别用于酶谱法检测MMP-2和MMP-9活性,以及RT-PCR分析mRNA表达。结果内皮细胞与活化血小板共同培养后,酶谱法显示：与对照组相比,未活化的血小板轻微诱导MMP-2和MMP-9分泌,而活化状态的血小板能显著诱导这二者的分泌,与IL-1β的作用相当;而且还可以见到62kDaMMP-2活化形式。加入阻断剂GRGDSP以及GPⅡb/Ⅲa单克隆抗体（7E3）作用后检测发现,MMP-2和MMP-9分泌减少。与活化血小板共同培养后的内皮细胞表面表达uPAR和MT1-MMP以及上清液中MMP-2的mRNA与对照组相比明显增高,而静息状态的血小板作用不显著。加入GRGDSP或7E3后,mR-NA的表达降低。结论①活化状态的血小板与IL-1β的作用相当,能显著诱导MMP-2和MMP-9分泌;能明显增高内皮细胞（EC）-uPAR和MT1-MMP及上清液中MMP-2mRNA的表达;②GPⅡb/Ⅲa阻断剂可能抑制血小板在不稳定斑块部位聚集、粘附等一系列炎症反应。     

Association between serum levels of testosterone and biomarkers of subclinical atherosclerosis

Objective: To investigate the association between serum levels of testosterone and biomarkers of subclinical atherosclerosis based on data from 119 middle-aged men of the general population.

Methods: Testosterone, Apolipoprotein A-1 (ApoA-1), Apolipoprotein B (ApoB), Apolipoprotein B-to-Apolipoprotein A-1 ratio (ApoB-to-ApoA-1), high-sensitive C-reactive protein (hsCRP), and fibrinogen levels were measured. Data were also gathered based on age, BMI, waist circumference, smoking, alcohol consumption, and family history of cardiovascular diseases. Men were classified into two groups based on testosterone levels: hypogonadal (testosterone ≤12?nmol/L) and eugonadal men (testosterone >12?nmol/L).

Results: When compared to eugonadal, the hypogonadal men were significantly older (56?years vs. 55?years, p?=?.03), had greater BMI (28?kg/cm² vs. 26?kg/cm², p?=?.01), and higher waist circumference (104?cm vs. 100?cm, p?=?.01). Moreover, ApoB, ApoB-to-ApoA-1 ratio, and hsCRP were significantly higher in hypogonadal men compared to eugonadal men (1.1?g/L vs. 1.0?g/L, p?=?.03), (0.8 vs. 0.7, p?=?.03), (3.3?mg/L vs. 2.0?mg/L, p?=?.01), respectively. On the other hand, ApoA-1 and fibrinogen levels did not differ significantly between groups (p?>?.05). In an adjusted multivariate regression analysis model, only ApoB showed a significant negative association with testosterone levels (β?=??0.01; 95% CI?=??0.02, ?1.50; p?=?.04).

Conclusion: Testosterone levels showed an inverse relation to ApoB, a biomarker implicated in subclinical atherosclerosis. These findings support the hypothesis that low testosterone levels play a role in atherosclerosis.     

The impact of atherosclerosis on lower urinary tract function

Abstract

Objective: The current study was carried out to investigate the impact of atherosclerosis on lower urinary tract function in the male patients with lower urinary tract symptoms (LUTS).

Patients and methods: This prospective study evaluated 110 male patients aged 55–75 years who were presented with LUTS. All patients underwent general and local investigations. The atherosclerosis was assessed by ultrasound examination of the carotid artery. Patients then were divided into two groups: non-atherosclerosis group (Group 1) and atherosclerosis group (Group 2). The two groups were compared regarding voiding and storage parameters.

Results: Mean patient age were 67.9?±?5.9 years. The average age and number of Group 1 was 65.7?±?4.3, n?=?51. The average age and number of Group 2 was 68.7?±?5.3, n?=?59. There were no significant differences in age, prostate volume, blood pressure, International Prostate Symptom Score, Voiding symptom score and Storage symptom score between the two groups. Blood serum triglycerides were significantly lower in Group 1 than Group 2 while HDL cholesterol were significantly higher in Group 1 than Group 2 0.97?±?0.5 and 1.43?±?0.2?mmol/L, versus 1.46?±?0.7 and 1.28?±?0.3?mmol/L, respectively. Qmax denotes significant decrease in Group 2 compared with Group 1 12.5?±?6.3 versus 17.6?±?6.5, respectively (p?<?0.01). While in post-voiding residual urine, there was a significant increase in Group 2 compared with Group 1 82.2?±?15.4 versus 51.4?±?12.7, respectively (p?<?0.01). Daytime voided urine denotes a significant decrease in Group 2 176?±?48, compared with Group 1 221.2?±?79 (p?<?0.01). Daytime frequency and nocturia, were significantly higher in Group 2, compared with Group 1 8.90?±?2.8 versus 7.16?±?3.11, respectively, and 3.1?±?1.2 versus 1.92?±?1.12, respectively (p?<?0.05).

Conclusion: The atherosclerosis disease play a significant role in the impairments of both voiding and storage function in male patients with LUTS irrelevant to the age.     

瑞舒伐他汀对高脂饮食家兔动脉粥样硬化斑块及血脂的影响

目的探讨瑞舒伐他汀对高胆固醇饮食家兔颈动脉粥样硬化斑块内细胞半胱氨酸天冬氨酸蛋白-9（Caspase-9）和增殖细胞核抗原（PCNA）表达及血脂的影响。方法采用高脂饮食喂养法建立动脉粥样硬化模型,24只家兔随机分为：对照组8只（普通饲料）、模型组8只（普通饲料＋2%胆固醇）、治疗组8只[普通饲料＋2%胆固醇＋瑞舒伐他汀0.1mg/（kg·d）],12周后处死。结果模型组、治疗组血清TC、TG、LDL-C值明显高于对照组,治疗组明显低于模型组（P〈0.05）。病理结果显示：治疗组光镜下见斑块明显减小,血管内膜斑块细胞数减少、纤维化。免疫组化结果显示：治疗组与模型组相比Caspase-9阳性细胞数明显增多,具有统计学差异（P〈0.05）,而PCNA阳性细胞数明显少于模型组（P〈0.05）。结论瑞舒伐他汀能明显调整脂质代谢,并可通过增强Caspase-9蛋白表达,诱导动脉粥样斑块内细胞的凋亡;下调PCNA蛋白的表达,抑制细胞增殖,抑制动脉粥样斑块发展、稳定斑块从而达到治疗效果。     

同型半胱氨酸与动脉粥样硬化

动脉粥样硬化(AS)是心脑血管疾病重要的病理基础。高半胱氨酸血症(HH)是AS独立的危险因素。预防HH对延缓动脉粥样硬化的发生、发展,降低心脑血管病的发病率、致残率和病死率有着重要的意义。