尼古丁预防帕金森氏综合症和老年痴呆症的分子机理研究

吸烟有害健康,吸烟产生的自由基、亚硝胺和多环芳烃等是主要有害物质,而尼古丁是造成吸烟依赖的主要物质。流行病学统计显示,吸烟者患帕金森氏综合症(Parkinson's disease,PD)和老年痴呆症(Alzheimer's disease,AD)的概率远低于不吸烟者;实验和人群结果表明尼古丁可以预防PD和AD,但其机理还不十分清楚。实验发现:1)尼古丁可以有效清除活性氧自由基,能够抑制多巴胺自氧化,是一种抗氧化剂;2)尼古丁能够有效抑制6-OHDA和MPP 诱导的细胞色素C(Cytochrome C,Cyt.C)释放;3)尼古丁可以保护海马神经元抵抗β淀粉样蛋白诱导的凋亡;4)尼古丁可以防止淀粉样蛋白在转基因AD鼠脑中的沉淀;5)尼古丁可以络合金属铜和锌,防止其在脑中积聚;6)尼古丁可以通过激活烟碱型乙酰胆碱受体nAChRs(nicotin acetylcholine receptor)7和MAPK(mitogen activated protein kinase)来抑制NF-κB和C-Myc信号通路,抑制炎症和诱导型NOS表达和NO生成,预防AD。这些结果对于解释尼古丁防治神经退行性疾病AD和PD的机理具有重要意义。     

The Study of Cu and Zn Serum Levels in Idiopathic Dilated Cardiomyopathy (IDCMP) Patients and its Comparison with Healthy Volunteers

Changes in the cupper (Cu) and zinc (Zn) concentrations have been reported previously in idiopathic dilated cardiomyopathy (IDCMP). As a result of controversial results, the aim of this study was to compare the Zn and Cu concentrations and Zn/Cu ratio of IDCMP patients to healthy volunteers. In addition, the correlation of Cu and Zn levels with age has been evaluated. The study population consisted of 18 IDCMP patients and 27 healthy volunteers. IDCMP patients had normal angiography with echocardiography supporting cardiomyopathy without pericardial and valvular diseases. Exclusion criteria were renal or hepatic insufficiency, alcohol usage, and intake of supplements containing Cu or Zn within 1 week ago. Cu and Zn levels have been assayed with atomic absorption spectrophotometry. Statistical analysis was performed with SPSS 10 software with independent sample t test for comparing the level of Cu and Zn of IDCMP patients with normal subjects and Pearson correlation to determine the correlation between numeric data. P < 0.05 was considered as significant differences. There was a trend for a lower Zn level in IDCMP patients compared to healthy volunteers. (0.97 ± 0.25 mg/l vs. 1.12 ± 0.42 mg/l, respectively). The mean Cu levels of IDCMP and normal subjects were 1.33 ± 0.20 mg/l and 1.31 ± 0.23 mg/l, respectively. There was a significant difference in Zn/Cu ratio among patients based on the NYHA classification of heart failure (P = 0.003). Age was negatively correlated with Zn levels in IDCMP group (P = 0.037) and positively with Cu levels in healthy volunteers (P = 0.012). A lower Zn level in IDCMP patients compared to healthy volunteers and specially a significant difference in Zn/Cu ratio of patients based on their NYHA classification would suggest a critical role of zinc and Cu imbalance in development of IDCMP.