目的研究合并高血压病的老年女性骨质疏松患者口服维生素K2联合咪达普利对骨密度(bone mineral density,BMD)、骨代谢、新发骨折率及不良反应的影响。方法选择2018年7月至2019年8月石家庄市第一医院收治的合并高血压的老年女性骨质疏松...目的研究合并高血压病的老年女性骨质疏松患者口服维生素K2联合咪达普利对骨密度(bone mineral density,BMD)、骨代谢、新发骨折率及不良反应的影响。方法选择2018年7月至2019年8月石家庄市第一医院收治的合并高血压的老年女性骨质疏松患者40例为研究对象,随机分为观察组、对照组,各20例,对照组服用咪达普利,观察组在此基础上加服四烯甲萘醌软胶囊。6个月后,观察两组患者新发骨折率、不良反应率,测定血清骨代谢指标和腰及髋部BMD的水平。结果治疗6个月后,与治疗前相比两组25(OH)D3增加、PTH下降(P<0.05),两组OC、BAP及各处BMD升高,TRACP-5b、s-CTX降低(P<0.001);与对照组相比,观察组BAP、OC更高,TRACP-5b、s-CTX更低,经校正P<0.001;与对照组相比,观察组腰椎、股骨颈BMD较高(P<0.05),△BMD差异有统计学意义(P<0.001);协方差校正股骨粗隆BMD及△BMD两组间比较差异有统计学意义(P<0.05);观察组治疗前BMD同治疗后BMD水平呈线性相关(P<0.001),BMD水平治疗前、后回归线斜率(b)不同。新发骨折率及不良反应率组间对比差异无统计学意义(P>0.05)。结论①维生素K2及咪达普利对合并高血压的老年女性骨质疏松患者联合用药效果有叠加作用,对骨代谢及骨密度有更好的改善作用;②联合用药对身体各处骨密度改善水平并不一致,骨密度基线水平可能对骨密度改善的曲线存在影响。展开更多
Objective To investigate the long-term effects of imidapril (IMI) on action potential and calcium and potassium currents in rabbit left ventricular hypertrophic myocytes. Methods Rabbits were randomly divided into th...Objective To investigate the long-term effects of imidapril (IMI) on action potential and calcium and potassium currents in rabbit left ventricular hypertrophic myocytes. Methods Rabbits were randomly divided into three groups: IMI-treated, hypertrophic and sham-operated control groups. Cardiac hypertrophy was induced in hypertrophy group by partial ligation of the abdominal aorta. In the IMI-treated group, the rabbits were administered IMI (1.5 mg·kg -1·d -1) for 8 weeks after surgery. In the sham-operated control group, the animals underwent an abdominal laparotomy without further procedure. Whole-cell patch clamp technique was used to record ionic currents. Results Membrane capacitance was larger in hypertrophic cells than in sham-operated cells or IMI-treated cells. Action potential duration was lengthened in hypertrophic cells and was remarkably shortened by IMI. The density of I Ca,L was reduced from 12.8±0.7 pA/pF in the sham-operated cells, to 7.7±0.8 pA/pF in hypertrophic cells, while it resembled the control cells after IMI treatment (11.9±1.0 pA/pF). After IMI treatment, the density of I Ks,tail was enhanced from 2.5±0.1 pA/pF in hypertrophic cells to 4.7±0.6 pA/pF (n=7, P<0.01), which was similar to the sham-operated cells. The densities of I to and I K1 were significantly increased in IMI-treated cells, from 3.8±0.4 pA/pF and 3.7±0.5 pA/pF in the hypertrophic cells to 6.4±0.8 pA/pF and 6.5±0.3 pA/pF, respectively, but the I Kr densities were not different in the three groups. Conclusion IMI could reverse the increase in membrane capacitance in hypertrophic cells, shorten action potential duration, and increase the densities of I Ca, L, I Ks, I to and I K1 in hypertrophic cells.展开更多
Carboxylesterases (CESs) play important roles in the metabolism of endogenous and foreign compounds in physiological and pharmacological responses. The aim of this study was to investigate the effect of dexamethasone ...Carboxylesterases (CESs) play important roles in the metabolism of endogenous and foreign compounds in physiological and pharmacological responses. The aim of this study was to investigate the effect of dexamethasone at different doses on the expression of CES1 and CES2. Imidapril and irinotecan hydrochloride (CPT-11) were used as special substrates for CES1 and CES2, respectively. Rat hepatocytes were cultured and treated with different concentrations of dexamethasone. The hydrolytic activity of CES1 and CES2 was tested by incubation experiment and their expression was quantitated by real-time PCR. A pharmacokinetic study was conducted in SD rats to further evaluate the effect of dexamethasone on CESs activity in vivo. Western blotting was performed to investigate the regulatory mechanism related to pregnane X receptor (PXR) and glucocorticoid receptor (GR). The results showed that exposure of cultured rat hepatocytes to nanomolar dexamethasone inhibited the imidapril hydrolase activity, which was slightly elevated by micromolar dexamethasone. For CES2, CPT-11 hydrolase activity was induced only when dexamethasone reached micromolar levels. The real-time PCR demonstrated that CES1 mRNA was markedly decreased by nanomolar dexamethasone and increased by micromolar dexamethasone, whereas CES2 mRNA was significantly increased by micromolar dexamethasone. The results of a complementary animal study showed that the concurrent administration of dexamethasone significantly increased the plasma concentration of the metabolite of imidapril while the ratio of CPT-11 to its metabolite SN-38 was significantly decreased. PXR protein was gradually increased by serial concentrations of dexamethasone. However, only nanomolar dexamethasone elevated the level of GR protein. The different concentrations of dexamethasone required suggested that suppression of CES1 may be mediated by GR whereas the induction of CES2 may result from the role of PXR. It was concluded that dexamethasone at different concentrations can differentially reg展开更多
文摘目的研究合并高血压病的老年女性骨质疏松患者口服维生素K2联合咪达普利对骨密度(bone mineral density,BMD)、骨代谢、新发骨折率及不良反应的影响。方法选择2018年7月至2019年8月石家庄市第一医院收治的合并高血压的老年女性骨质疏松患者40例为研究对象,随机分为观察组、对照组,各20例,对照组服用咪达普利,观察组在此基础上加服四烯甲萘醌软胶囊。6个月后,观察两组患者新发骨折率、不良反应率,测定血清骨代谢指标和腰及髋部BMD的水平。结果治疗6个月后,与治疗前相比两组25(OH)D3增加、PTH下降(P<0.05),两组OC、BAP及各处BMD升高,TRACP-5b、s-CTX降低(P<0.001);与对照组相比,观察组BAP、OC更高,TRACP-5b、s-CTX更低,经校正P<0.001;与对照组相比,观察组腰椎、股骨颈BMD较高(P<0.05),△BMD差异有统计学意义(P<0.001);协方差校正股骨粗隆BMD及△BMD两组间比较差异有统计学意义(P<0.05);观察组治疗前BMD同治疗后BMD水平呈线性相关(P<0.001),BMD水平治疗前、后回归线斜率(b)不同。新发骨折率及不良反应率组间对比差异无统计学意义(P>0.05)。结论①维生素K2及咪达普利对合并高血压的老年女性骨质疏松患者联合用药效果有叠加作用,对骨代谢及骨密度有更好的改善作用;②联合用药对身体各处骨密度改善水平并不一致,骨密度基线水平可能对骨密度改善的曲线存在影响。
文摘Objective To investigate the long-term effects of imidapril (IMI) on action potential and calcium and potassium currents in rabbit left ventricular hypertrophic myocytes. Methods Rabbits were randomly divided into three groups: IMI-treated, hypertrophic and sham-operated control groups. Cardiac hypertrophy was induced in hypertrophy group by partial ligation of the abdominal aorta. In the IMI-treated group, the rabbits were administered IMI (1.5 mg·kg -1·d -1) for 8 weeks after surgery. In the sham-operated control group, the animals underwent an abdominal laparotomy without further procedure. Whole-cell patch clamp technique was used to record ionic currents. Results Membrane capacitance was larger in hypertrophic cells than in sham-operated cells or IMI-treated cells. Action potential duration was lengthened in hypertrophic cells and was remarkably shortened by IMI. The density of I Ca,L was reduced from 12.8±0.7 pA/pF in the sham-operated cells, to 7.7±0.8 pA/pF in hypertrophic cells, while it resembled the control cells after IMI treatment (11.9±1.0 pA/pF). After IMI treatment, the density of I Ks,tail was enhanced from 2.5±0.1 pA/pF in hypertrophic cells to 4.7±0.6 pA/pF (n=7, P<0.01), which was similar to the sham-operated cells. The densities of I to and I K1 were significantly increased in IMI-treated cells, from 3.8±0.4 pA/pF and 3.7±0.5 pA/pF in the hypertrophic cells to 6.4±0.8 pA/pF and 6.5±0.3 pA/pF, respectively, but the I Kr densities were not different in the three groups. Conclusion IMI could reverse the increase in membrane capacitance in hypertrophic cells, shorten action potential duration, and increase the densities of I Ca, L, I Ks, I to and I K1 in hypertrophic cells.
基金supported by a grant from the Natural Science Foundation of Hubei Province of China(No.2011CD-B550)
文摘Carboxylesterases (CESs) play important roles in the metabolism of endogenous and foreign compounds in physiological and pharmacological responses. The aim of this study was to investigate the effect of dexamethasone at different doses on the expression of CES1 and CES2. Imidapril and irinotecan hydrochloride (CPT-11) were used as special substrates for CES1 and CES2, respectively. Rat hepatocytes were cultured and treated with different concentrations of dexamethasone. The hydrolytic activity of CES1 and CES2 was tested by incubation experiment and their expression was quantitated by real-time PCR. A pharmacokinetic study was conducted in SD rats to further evaluate the effect of dexamethasone on CESs activity in vivo. Western blotting was performed to investigate the regulatory mechanism related to pregnane X receptor (PXR) and glucocorticoid receptor (GR). The results showed that exposure of cultured rat hepatocytes to nanomolar dexamethasone inhibited the imidapril hydrolase activity, which was slightly elevated by micromolar dexamethasone. For CES2, CPT-11 hydrolase activity was induced only when dexamethasone reached micromolar levels. The real-time PCR demonstrated that CES1 mRNA was markedly decreased by nanomolar dexamethasone and increased by micromolar dexamethasone, whereas CES2 mRNA was significantly increased by micromolar dexamethasone. The results of a complementary animal study showed that the concurrent administration of dexamethasone significantly increased the plasma concentration of the metabolite of imidapril while the ratio of CPT-11 to its metabolite SN-38 was significantly decreased. PXR protein was gradually increased by serial concentrations of dexamethasone. However, only nanomolar dexamethasone elevated the level of GR protein. The different concentrations of dexamethasone required suggested that suppression of CES1 may be mediated by GR whereas the induction of CES2 may result from the role of PXR. It was concluded that dexamethasone at different concentrations can differentially reg
