摘要
目的:研究川芎嗪(TMP)对大鼠海马神经元细胞膜L型钙通道电流(Ica.L)的作用和对神经细胞内钙([Ca2+]i)的影响,探讨其治疗阿尔茨海默病(Alzhei mer disease,AD)的机制。方法:在原代培养大鼠海马神经元的基础上,使用全细胞膜片钳技术联合激光扫描共聚焦显微镜观察TMP对神经元Ica.L和[Ca2+]i的影响。结果:①膜片钳证实,3、10、30、100 mg/L的TMP处理组能显著抑制细胞膜L型钙通道电流(Ica.L)峰值,分别由对照组的(550.21±26.27)pA降至(380.18±16.25)pA、(302.11±13.92)pA、(203.57±11.65)pA和(121.58±9.87)pA(P<0.01),使I-V曲线上移,且具有浓度依赖性,但对最大激活电位无明显影响;②激光扫描共聚焦显微镜测量发现,细胞外液为有钙液和无钙液时;③10、30和100 mg/L TMP预处理组均能显著抑制60 mmol/L的KCL引起的细胞内钙荧光峰值(Fi)增加,且有钙液和无钙液组荧光强度变化率(Fi/Fo)比较有统计学意义(P<0.05)。结论:TMP具有对海马神经元L-Ca2+通道和细胞内钙库释放的双重抑制作用,防治神经元细胞内钙超载,这可能是其治疗AD的机制之一。
Objective:To observe the effect and mechenism of TMP on L-type calcium current and the intracellular calcium concentration of hippocampal neuronal cells on Alzheimer disease(AD) Method.. Whole cell patch clamp technique was used to record the currents of L Type calcium channels in primary cultured hippocampal neuronal cells, and [Ca^2+]i was measured by laser scanning confocal microscope. Result: (1)It was conformed by patch--clamp technique that TMP with concentrations of 3,10,30,100 mg/ml can inhibit Ica. L concentration-dependently, control group's peak value of Ica. L was reduced to (380. 18 ± 16. 25)pA. (302. 11± 13. 92)pA. (203.57±11.65)pA.and(121.58±9.87)pA from(550.21±26.27)pA( P 〈0.01),and the I-V curves of Ica. L shifted upwardly. (2) Whether extracellular solution with or without calcium, four different concentrations of TMP can reduce the elevation of [Ca^2+]i induced by 60 mmol/L KCl solution,and two groups compare with each other has apparent difference( P〈0. 05). Conclusion: Both Ica. L channel and the release of intracellular calcium store can be inhibited by TMP,this is possibly one of its mechanisms in therapeutic role in AD.
出处
《临床急诊杂志》
CAS
2009年第6期332-335,共4页
Journal of Clinical Emergency
关键词
川芎嗪
阿尔茨海默病
telramethylpyraze
Alzheimer disease