丙泊酚抑制去甲肾上腺素诱导大鼠肺动脉平滑肌细胞内游离钙浓度升高作用的机理

用荧光分光光度法及同位素放射免疫分析法检测丙泊酚(30-300 μmol·L^-1)影响大鼠肺动脉平滑肌细胞(PASMC)内游离钙离子浓度(［Ca²⁺］_i)与肌醇-1，4，5-三磷酸(IP₃)合成作用，以探讨丙泊酚舒张肺动脉平滑肌的作用机理.结果表明，与丙泊酚共同培养72 h，对PASMC ［Ca²⁺］_i 基础水平无明显影响，但可浓度依赖性抑制去甲肾上腺素(NE 3 μmol·L^-1)引起的［Ca²⁺］_i升高作用；当细胞外液无钙或存在钙通道阻滞剂维拉帕米(30 μmol·L^-1)时，丙泊酚抑制NE升高［Ca²⁺］_i作用被增强；丙泊酚还可浓度依赖性抑制NE促进 IP₃合成作用. 结果提示丙泊酚舒张血管平滑肌作用与抑制IP₃介导的细胞内钙释放密切相关.

Mechanism of propofol inhibiting norepinephrine-induced levation of intracellular free calcium in pulmonary artery smooth muscle cells of rat

To probe into the mechanism of propofol on the relaxation of the vascular smooth muscle, the effects of propofol (30-300 μmol·L^-1) on intracellular free calcium concentration (［Ca²⁺］_i) and inositol-1,4,5-triphosphate (IP₃) biological synthesis induced by norepinephrine (NE 3 μmol·L^-1) in pulmonary artery smooth muscle cells (PASMC) in rats were examined by using the spectrofluorometry and radioimmunoassay. The results showed that: (1) when primary cultured PASMC were pretreated with propofol for 72 h the basic levels of ［Ca²⁺］_i did not change obviously, but the NE induced ［Ca²⁺］_i increase was concentration dependently inhibited. (2) When in the extracellular calcium free medium or in the calcium channel blocker (verapamil 30 mmol·L^-1) medium, the inhibition of propofol on NE-induced ［Ca²⁺］_i increase was enhanced. (3) Propofol inhibited IP₃ biological synthesis induced by NE in the concentration-dependent manner. These results suggest that the relaxation of propofol on pulmonary artery smooth muscle be closely related to decrease of ［Ca²⁺］_i through mechanism of IP3 induced calcium release.