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目的研究MN9202对Forskolin(腺苷酸环化酶激动剂)、盐酸四乙胺(TEA,钙激活钾通道阻断剂)和美蓝(MB,鸟苷酸环化酶抑制剂)增强心肌细胞收缩、舒张功能影响的机制。方法采用IonOptix单细胞动缘检测系统(IonOptixCo.USA),测定心肌细胞收缩幅度和收缩/舒张速度等。这些指标均由计算机自动实时采集并记录。结果Forskolin、MB和TEA增强心肌细胞收缩幅度(ph)和心肌细胞收缩幅度/单个心肌细胞的长度百分比(ph/bl%),最大缩短速率(+dL/dt)和最大复长速率(-dL/dt),Forskolin和MB增强上述指标均有显著性差异(P<0.01)。Forskolin通过cAMP的增加发挥作用。MB通过减少cGMP的生成使心肌细胞的收缩功能增强。Forskolin增加ph、ph/bl%、+dL/dt和-dL/dt,上述指标分别增加91%、123%、110%、89%,用MB后,ph、ph/bl%、+dL/dt和-dL/dt分别为0.14±0.04μm、11±4%、2.2±0.3μm/s和2.2±0.6μm/s,用药前后差异非常显著(P<0.01)。3×10-6mol/L的MN9202降低Forskolin引起ph、ph/bl%、+dL/dt和-dL/dt的升高,其中+dL/dt和-dL/dt的降低较对照组显著差异。同时MN9202能降低MB和TEA引起ph、ph/bl%、+dL/dt和-dL/dt的增加。结论Forskolin、TEA和MB使心肌细胞收缩和舒张功能均增强,Forskolin能直接增加细胞内钙,TEA和MB能间接使细胞内钙增加而增强收缩功能;MN9202有抑制Forskolin、TEA和MB的作用。
Objective To investigate the effect of MN9202 on cardiomyocyte contraction induced by Forskolin (adenylate cyclase agonist), tetraethylammonium hydrochloride (TEA, calcium activated potassium channel blocker) and methylene blue (MB, guanylate cyclase inhibitor) Mechanism of diastolic function. Methods IonOptix single cell kinetic detection system (IonOptixCo.USA) was used to measure the contractile / systolic velocity of cardiomyocytes. These indicators are automatically collected by the computer in real time and recorded. Results Forskolin, MB and TEA increased cardiomyocyte contraction amplitude (ph) and cardiomyocyte contraction amplitude / percentage of single cardiomyocyte length (ph / bl%), maximum shortening rate (+ dL / dt) and maximum growth rate / dt), Forskolin and MB enhanced the above indicators were significantly different (P <0.01). Forskolin works by increasing cAMP. MB enhances cardiomyocyte contractile function by reducing cGMP production. Forskolin increased ph, ph / bl%, + dL / dt and -dL / dt, respectively. The above indexes were increased by 91%, 123%, 110% and 89% And -dL / dt were 0.14 ± 0.04μm, 11 ± 4%, 2.2 ± 0.3μm / s and 2.2 ± 0.6μm / s respectively. There was significant difference before and after treatment (P <0.01). 3 × 10-6mol / L MN9202 could reduce the increase of ph, ph / bl%, + dL / dt and -dL / dt induced by Forskolin. The decrease of + dL / dt and -dL / dt were significantly different from the control group. At the same time MN9202 can reduce the increase of ph, ph / bl%, + dL / dt and -dL / dt caused by MB and TEA. Conclusion Forskolin, TEA and MB can enhance the contractile and diastolic functions of cardiomyocytes. Forskolin can directly increase the intracellular calcium. TEA and MB indirectly increase the intracellular calcium and enhance the contractile function. MN9202 can inhibit the effect of Forskolin, TEA and MB.