目的比较非肽类血管紧张素Ⅱ受体Ⅰ型阻断剂氯沙坦(Losartan)和血管活性肽降钙素基因相关肽(CGRP)对血管紧张素Ⅱ诱导的血管平滑肌细胞增殖作用的影响,为探讨此两类物质的降压机制提供实验依据。方法采用MTT,3H-参入法和流式细胞仪分别...目的比较非肽类血管紧张素Ⅱ受体Ⅰ型阻断剂氯沙坦(Losartan)和血管活性肽降钙素基因相关肽(CGRP)对血管紧张素Ⅱ诱导的血管平滑肌细胞增殖作用的影响,为探讨此两类物质的降压机制提供实验依据。方法采用MTT,3H-参入法和流式细胞仪分别测定血管紧张素Ⅱ刺激下,Losartan或CGRP干预下血管平滑肌细胞的增殖变化,W est-ern b loting法测定不同状态下血管平滑肌细胞内ERK1/2的活性变化。结果Losartan或CGRP能抑制血管紧张素Ⅱ刺激下血管平滑肌细胞的生存率、DNA合成、细胞周期增殖指数,以及细胞内ERK1/2的活性,并呈剂量依赖性。而且,CGRP抑制作用强于Losartan。结论Losartan或CGRP能抑制血管紧张素Ⅱ刺激下血管平滑肌细胞增殖,其细胞内的信号传导途径与ERK1/2有关。展开更多
目的 探讨氯沙坦降低癫痫大鼠共患抑郁症风险的有效性及相关机制。方法 雄性SD大鼠随机分为3组,每组8只:匹罗卡品-氯沙坦(pilocarpine and losartan,PL-L)组接受锂-匹罗卡品腹腔注射建模,后给予氯沙坦干预;匹罗卡品(pilocarpine,PL)组...目的 探讨氯沙坦降低癫痫大鼠共患抑郁症风险的有效性及相关机制。方法 雄性SD大鼠随机分为3组,每组8只:匹罗卡品-氯沙坦(pilocarpine and losartan,PL-L)组接受锂-匹罗卡品腹腔注射建模,后给予氯沙坦干预;匹罗卡品(pilocarpine,PL)组接受锂-匹罗卡品腹腔注射建立癫痫大鼠模型;对照(control,Ctrl)组接受氯化锂腹腔注射。采用体质量增长量和蔗糖偏爱实验对大鼠进行行为学分析,并采用RT-PCR检测大鼠海马区高迁移率族蛋白B1(high-mobility group protein B1,HMGB1)、白介素-1β(interleukin-1β,IL-1β)、白介素-6(interleukin-6,IL-6)mRNA的相对表达量。结果 PL组大鼠与Ctrl组相比,出现体质量增长量[(12.68±5.23)g vs.(41.08±15.87)g,P<0.01]和糖水偏爱率(53.85%±10.14%vs. 88.56%±16.53%, P<0.01)下降,大鼠海马区HMGB1 mRNA相对表达量增加(4.17±1.23 vs. 1.00±0.02, P<0.01),同时IL-1β(4.95±1.67 vs. 1.02±0.27, P<0.01)、IL-6(2.75±1.20 vs. 1.01±0.19, P<0.05)mRNA相对表达量也增加;PL-L组大鼠与PL组相比,体质量增长量[(37.97±10.24)g vs.(12.68±5.23)g, P<0.01]和糖水偏爱率(77.50%±7.35%vs. 53.85%±10.14%, P<0.05)增加,海马区HMGB1 mRNA相对表达量下降(0.76±0.27 vs. 4.17±1.23, P <0.01),同时IL-1β(0.67±0.21 vs. 4.95±1.67, P<0.01)、IL-6(0.95±0.27 vs. 2.75±1.20, P<0.05)mRNA相对表达量也下降。结论 氯沙坦可以减少癫痫大鼠共患抑郁症的发生,其可能的机制是氯沙坦减少HMGB1释放,从而减轻大鼠海马区炎症因子(IL-1β、IL-6)的表达,降低癫痫共患抑郁症的风险。展开更多
Aim To evaluate the bioequivalence of two brands of losartan/hydrochlorothiazide （50 mg/12.5 mg） compound tablets in healthy Chinese male volunteers. Methods An open, randomized, single-dose, two-period cross-over s...Aim To evaluate the bioequivalence of two brands of losartan/hydrochlorothiazide （50 mg/12.5 mg） compound tablets in healthy Chinese male volunteers. Methods An open, randomized, single-dose, two-period cross-over study with a wash-out period of 7 d was conducted. Twenty healthy male volunteers were given a single dose 50 mg losartan/12.5 mg hydrochlorothiazide of either test （T） or reference （R） compound tablets, respectively. Blood samples were collected up to 48 h after oral administration. The concentrations of losartan and hydrochlorothiazide in plasma were determined by a validated HPLC-ESI-MS method. Results In the case of losartan, the 90% confidence intervals of two one-side test for percent ratios with a significant level （α） of 0. 05 were 86% - 112% for AUC0-12 and 89% - 134% for Cmax, respectively, which were within the interval proposed in the Chinese Pharmacopoeia, 80% - 125% of AUC and 70% - 143% of Cmax, respectively. Similarly, the 90% confidence intervals for percent ratios were 85% - 100% and 75% - 102% for hydrochlorothiazide, both of which fell into the accepted interval. Conclusion Two immediate-release compound tablets of losartan/hydrochlorothiazide are bioequivalent from a statistical standpoint in the extent and rate of absorption from the single-dose study in healthy Chinese male volunteers.展开更多
文摘目的比较非肽类血管紧张素Ⅱ受体Ⅰ型阻断剂氯沙坦(Losartan)和血管活性肽降钙素基因相关肽(CGRP)对血管紧张素Ⅱ诱导的血管平滑肌细胞增殖作用的影响,为探讨此两类物质的降压机制提供实验依据。方法采用MTT,3H-参入法和流式细胞仪分别测定血管紧张素Ⅱ刺激下,Losartan或CGRP干预下血管平滑肌细胞的增殖变化,W est-ern b loting法测定不同状态下血管平滑肌细胞内ERK1/2的活性变化。结果Losartan或CGRP能抑制血管紧张素Ⅱ刺激下血管平滑肌细胞的生存率、DNA合成、细胞周期增殖指数,以及细胞内ERK1/2的活性,并呈剂量依赖性。而且,CGRP抑制作用强于Losartan。结论Losartan或CGRP能抑制血管紧张素Ⅱ刺激下血管平滑肌细胞增殖,其细胞内的信号传导途径与ERK1/2有关。
文摘目的 探讨氯沙坦降低癫痫大鼠共患抑郁症风险的有效性及相关机制。方法 雄性SD大鼠随机分为3组,每组8只:匹罗卡品-氯沙坦(pilocarpine and losartan,PL-L)组接受锂-匹罗卡品腹腔注射建模,后给予氯沙坦干预;匹罗卡品(pilocarpine,PL)组接受锂-匹罗卡品腹腔注射建立癫痫大鼠模型;对照(control,Ctrl)组接受氯化锂腹腔注射。采用体质量增长量和蔗糖偏爱实验对大鼠进行行为学分析,并采用RT-PCR检测大鼠海马区高迁移率族蛋白B1(high-mobility group protein B1,HMGB1)、白介素-1β(interleukin-1β,IL-1β)、白介素-6(interleukin-6,IL-6)mRNA的相对表达量。结果 PL组大鼠与Ctrl组相比,出现体质量增长量[(12.68±5.23)g vs.(41.08±15.87)g,P<0.01]和糖水偏爱率(53.85%±10.14%vs. 88.56%±16.53%, P<0.01)下降,大鼠海马区HMGB1 mRNA相对表达量增加(4.17±1.23 vs. 1.00±0.02, P<0.01),同时IL-1β(4.95±1.67 vs. 1.02±0.27, P<0.01)、IL-6(2.75±1.20 vs. 1.01±0.19, P<0.05)mRNA相对表达量也增加;PL-L组大鼠与PL组相比,体质量增长量[(37.97±10.24)g vs.(12.68±5.23)g, P<0.01]和糖水偏爱率(77.50%±7.35%vs. 53.85%±10.14%, P<0.05)增加,海马区HMGB1 mRNA相对表达量下降(0.76±0.27 vs. 4.17±1.23, P <0.01),同时IL-1β(0.67±0.21 vs. 4.95±1.67, P<0.01)、IL-6(0.95±0.27 vs. 2.75±1.20, P<0.05)mRNA相对表达量也下降。结论 氯沙坦可以减少癫痫大鼠共患抑郁症的发生,其可能的机制是氯沙坦减少HMGB1释放,从而减轻大鼠海马区炎症因子(IL-1β、IL-6)的表达,降低癫痫共患抑郁症的风险。
文摘Aim To evaluate the bioequivalence of two brands of losartan/hydrochlorothiazide （50 mg/12.5 mg） compound tablets in healthy Chinese male volunteers. Methods An open, randomized, single-dose, two-period cross-over study with a wash-out period of 7 d was conducted. Twenty healthy male volunteers were given a single dose 50 mg losartan/12.5 mg hydrochlorothiazide of either test （T） or reference （R） compound tablets, respectively. Blood samples were collected up to 48 h after oral administration. The concentrations of losartan and hydrochlorothiazide in plasma were determined by a validated HPLC-ESI-MS method. Results In the case of losartan, the 90% confidence intervals of two one-side test for percent ratios with a significant level （α） of 0. 05 were 86% - 112% for AUC0-12 and 89% - 134% for Cmax, respectively, which were within the interval proposed in the Chinese Pharmacopoeia, 80% - 125% of AUC and 70% - 143% of Cmax, respectively. Similarly, the 90% confidence intervals for percent ratios were 85% - 100% and 75% - 102% for hydrochlorothiazide, both of which fell into the accepted interval. Conclusion Two immediate-release compound tablets of losartan/hydrochlorothiazide are bioequivalent from a statistical standpoint in the extent and rate of absorption from the single-dose study in healthy Chinese male volunteers.
文摘目的 研究 L osartan对肾小球系膜细胞 (MCs)结缔组织生长因子 (CTGF)表达的影响。进一步探讨 L osartan延缓肾纤维化的机制。方法 将体外培养的 MCs分为 3组 :1正常对照组 ,未加任何刺激因素 ;2浓度为 10 - 5mol/L 的 Ang 组 ;3Ang 中加入 10 - 5m ol/L 的 L osartan组。分别刺激 MCs72小时后 ,提取细胞RNA,采用逆转录 -聚合酶链反应技术测定 MCs CTGF m RNA水平变化。结果 L osartan干预 72小时后 ,MCsCTGF m RNA表达水平较 Ang 组下降 2 5 .1%,但仍高于对照 ,为对照组的 1.95倍。结论 L osartan通过部分抑制 Ang 对 CTGF m RNA表达的诱导而有益于延缓肾纤维化的进展 ,这可能是 L osartan延缓肾纤维化的机制。
