摘要
目的观察小檗碱(Ber)对离体豚鼠结肠肠管和平滑肌细胞的作用及对小鼠肠道P物质(SP)表达的影响,探讨Ber治疗炎症性肠病的机制。方法采用肌力换能技术记录肠管收缩幅值的变化,用全细胞膜片钳技术测量单个平滑肌细胞大电导的钙离子依赖性钾电流(IBkca),并采用免疫组化技术观察SP的表达变化。结果Ber(0.3~100μmol/L)能剂量依赖性地抑制电刺激(EFS)和速激肽(NKA)诱发的结肠收缩运动,其IC50分别为64.1μmol/L和82.5μmol/L;Ber 6μmol/L可显著增加IBkca的幅值约(51±21)%(n=6,P<0.05)。连续灌胃给予Ber 10 mg/(kg.d),7 d后,小鼠结肠SP的表达明显减少(P<0.05)。结论Ber减少SP的合成释放,增强IBkca,减弱细胞外钙内流,从而抑制EFS和NKA诱发的肠管收缩,这可部分解释其在炎症性肠病中的治疗作用。
Objective To investigate the role of berberine(Ber) in neurokinin A(NKA)-induced mechanical activity of proximal colon smooth muscle in guinea-pig.Methods The contractile function of the guinea-pig proximal colon rings was assessed by measuring isometric force.The large conductance Ca^(2+)-activated K^(+) currents(I_(Bkca)) were recorded by using whole cell patch-clamp technique.The expression of substance P(SP) was detected by immunohistochemistry.Results Ber(0.3-100 μmol/L) could significantly suppress the contractive amplitude induced by electrical field stimulation(EFS,IC_(50)=64.1 μmol/L) and administration of NKA(IC_(50)=82.5 μmol/L),and Ber 6 μmol/L markedly enhanced(51±21% increment) the amplitudes of I_(Bkca).The expression of SP was decreased significantly(P<0.05) in proximal colon of mice after Ber was given for 7 days.Conclusion Ber exerts an inhibition effect on the extracellular Ca^(2+) influx and the synthesis and release of tachykinin by enhancing I_(Bkca), which may contribute to the inhibition of contraction induced by EFS and NKA.
出处
《华中科技大学学报(医学版)》
CAS
CSCD
北大核心
2006年第6期715-717,共3页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
关键词
小檗碱
速激肽
膜片钳
炎症性肠病
berberine
tachykinin
patch-clamp technique
inflammatory bowel disease