The signal transduction pathway in the proliferation of airway smooth muscle cells induced by urotensin Ⅱ

Background Human urotensin Ⅱ (UⅡ) is the most potent mammalian vasoconstrictor identified so far. Our previous study showed that UⅡ is a potent mitogen of airway smooth muscle cells (ASMC) inducing ASMC proliferation in a dose-dependent manner. The signal transduction pathway of UⅡ mitogenic effect remains to be clarified. This study was conducted to investigate the signal transduction pathway in the proliferation of ASMC induced by UⅡ. Methods In primary cultures of rat ASMCs, activities of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and calcineurin (CaN) induced by UⅡ were measured. The effect of CaN on PKC and MAPK was studied by adding cyclosporin A (CsA), a specific inhibitor of CaN. Using H7 and PD98059, inhibitors of PKC and MAPK, respectively, to study the effect of PKC and MAPK on CaN. The cytosolic free calcium concentration induced by UⅡ was measured using Fura-2/AM. Results UⅡ 10-7 mol/L stimulated ASMC PKC and MAPK activities by 44% and 24% (P<0.01), respectively, after incubating for 20 minutes. It increased CaN activity in a time-dependent manner, being 1.68 times as that of control for 24 hours (P<0.01). It promoted the cytosolic free calcium concentration increase of 18% (P<0.01). CsA 10-6 mol/L and H7 50 μmol/L inhibited UⅡ-stimulated CaN activity by 45% (P<0.01) and 21% (P<0.05), respectively, while PD98059 50 μmol/L had no effect on CaN activity (P>0.05). CsA 10-6 mol/L inhibited UⅡ-stimulated PKC activity by 14% (P<0.05), while having no effect on MAPK activity (P>0.05). Conclusions UⅡ increases cytosolic free calcium concentration and activates PKC, MAPK and CaN. The signal transduction pathway between PKC and CaN has cross-talk.     

Clinical Observation on the Treatment of Atrial Fibrillation with Amiodarone Combined with Shenmai Injection (参麦注射液)

Objective: To observe the therapeutic efficacy and safety of amiodarone combined with Shenmai Injection (参麦注射液) on atrial fibrillation. Methods: A total of 351 patients with atrial fibrillation caused by cardiovascular diseases and idiopathic atrial fibrillation were assigned to amiodarone group (control group, 128 cases) and amiodarone combined with Shenmai Injection group (treatment group, 223 cases). The patients in the control group received intravenous injection of 150 mg amiodarone in 10 min, followed by intravenous drip infusion at 1 mg /min and 6 h later at 0.5 mg /min until 48 h or cardioversion. The patients in the treatment group received the same treatment of amiodarone, while in addition, they received an injection of Shenmai Injection of 100 mL simultaneously. Blood pressure, ventricular rate, and cardioversion were observed. Results: The total efficiency rate was 98% (control group) and 99% (treatment group) (P0.05). The mean ventricular rate decreased 23% and 31% in the control group and the treatment group, respectively (P0.05). The mean cardioversion time of the two groups was 570±211 min and 351±123 min, respectively (P0.05). Only mild side effects were observed in both groups. Conclusion: Compared with amiodarone, amiodarone combined with Shenmai Injection takes effect more quickly with low side effects on the treatment of atrial fibrillation.     

Effect of Shenmai Injection(参麦注射液)on Ventricular Diastolic Function in Patients with Chronic Heart Failure:An Assessment by Tissue Doppler Imaging

<正>Objective:To assess the effect of Shenmai Injection(参麦注射液,SMI) on left ventricular diastolic function(LVDF) in patients with chronic heart failure(CHF) by tissue Doppler imaging(TDI).Methods:Sixty-four CHF patients were randomly assigned to two groups,the observation group and the control group.Basic treatment including polarized liquid therapy was given to all the patients.In addition,SMI was given to patients of the observation group.The treatment duration was 14 days.TDI was performed in all the patients 3 days prior to the initiation of the treatment and one week after the medication to measure the average movement velocity of the mitral ring of the left ventricle at the early systolic stage and late diastolic stage(Ea and Aa);the outcomes were compared with the corresponding parameters obtained from blood flow Doppler echocardiography, namely,the velocity of the E-wave(E) and A-wave(A).Results:After treatment,Ea and Ea/Aa increased and Aa decreased significantly in the observation group(P0.05).In the control group,although some improvement was seen,there was no statistically significant change(P0.05).No statistical significance was shown between groups in these parameters after treatment.Conclusion:TDI assessment shows that SMI could effectively improve the LVDF in CHF patients.     

p-ERKl/2及ERK2mRNA在哮喘大鼠气道中的表达变化

目的 探讨细胞外信号调节激酶在哮喘大鼠气道中表达变化及其对气道平滑肌细胞增殖的影响.观察细胞外信号调节激酶是否参与了哮喘气道重构这一病理过程.方法 18只6周龄雄性wistar大鼠随机分为对照组、哮喘组、地塞米松干预组各6只.以腹腔注射10%卵蛋白和1%卵蛋白雾化吸入复制慢性哮喘模型.干预组在每次激发前给予地塞米松干预.用免疫组化与原位杂交法检测p-ERK1/2及ERK2 mRNA在不同大鼠肺组织的表达程度,采用图像分析系统进行图象分析.结果 (1)哮喘模型组气道壁面积和平滑肌厚度较对照组和干预组显著增加(P<0.05).(2)哮喘组p-ERK1/2及ERK2 mRNA在大鼠肺组织的表达程度较对照组和干预组显著增加(P<0.05).(3)直线相关性分析显示,哮喘组气道壁面积和平滑肌厚度与大鼠肺组织中p-ERK1/2表达水平呈正相关(分别为r=0.858,r=O.848,P均<0.05),哮喘组气道壁面积和平滑肌厚度与大鼠肺组织中ERK2 mRNA表达水平呈正相关,(分别为r=O.918,r=0.860,P均<0.05).结论 哮喘大鼠肺组织p-ERK1/2及ERK2 mRNA表达上调,并与气道重构密切相关,该结果提示细胞外信号调节激酶可能参与了气道重构中平滑肌的增殖过程.