ABSTRACT
OBJECTIVE：To evaluate the effects of nicorand il on the proliferation ，migration ability and Hippo/YAP signaling pathway of pulmonary artery smooth muscle cells （PASMCs）. METHODS ：Human primary PASMCs were divided into normal control group ，model group ，nicorandil low ，medium and high concentration groups （50，100，200 μmol/L），with 3 holes in each group. In addition to the normal control group ，the rest of the cells were inoculated on the gel coated medium to simulate the pulmonary hypertension environment ，so as to establish AS cell model. Then ，each drug group was added with corresponding drugs，and the normal control group and model group were added with the same volume of normal saline ，and cultured for 48 h. CCK-8 assay and Transwell assay were used for the examination of cell proliferation （by light density ）and migration ability ， respectively. mRNA expression of YAP target factors （CTGF and AREG ）were examined by qRT-PCR. Western blotting assay was used to detect the protein expression of CTGF and AREG. RESULTS ：Compared with normal control group ，light density of cells was increased significantly in model group ；the number of migration cells per field of view increased significantly ；mRNA and protein expression of CTGF and AREG were significantly increased （P＜0.01）. Compared with model group ，light density ，the number of migration cells per field of view ，mRNA and protein expression of CTGF and AREG in nicorandil low ，medium and high concentration groups were decreased significantly ， in concentration-dependent manner （P＜0.05 or P＜0.01）. CONCLUSIONS：Nicorandil can inhibit the proliferation and migration of PASMCs in AS model ，the mechanism of which cstc2019jscx-msxmX0174） may be associated with the Hippo/YAP signaling pathway.
ABSTRACT
Objective To observe the effect of blood pressure variability in patients with hypertension treated by amlodipine combined with perindopril.Methods From September 2012 to October 2013,patients with essential hypertension were given amlodipine 5 mg/d for 4 weeks,and 78 patients with blood pressure not reaching the standard after 4 weeks treatment were divided into group A and group B by random number table method,with 39 cases in each.Group A was given amlodipine 10 mg/d,and group B was given perindopril 4 mg/d on this basis (amlodipine 5 mg/d).Twenty-four hour ambulatory blood pressure was monitored in 2 groups by noninvasive portable ambulatory blood pressure monitoring in medication and 8 weeks after medication,measured values of standard deviation and coefficient of variation was used as a measurement of blood pressure variability.Results After 8 weeks of medication plus,24 h systolic blood pressure variability (24 h SSD),systolic blood pressure variability during the day (dSSD),nocturnal systolic blood pressure variability (nSSD),nocturnal systolic blood pressure variation coefficient (nSCV) and 24 h diastolic blood pressure variability(24 h DSD),diastolic blood pressure variability during the day (dDSD),nocturnal diastolic blood pressure variability (nDSD) in group A were significantly lower than those before medication plus[(13.22 ± 1.10) mmHg(1 mmHg =0.133 kPa) vs.(15.97 ± 1.65) mmHg,(12.04 ± 2.21) mmHg vs.(15.15 ±2.89) mmHg,(10.22 ±3.29) mmHg vs.(12.23 ±3.21) mmHg,0.093 ±0.021 vs.0.104 ± 0.017,(11.33 ± 2.09) mmHg vs.(13.27 ± 1.43) mmHg,(10.64 ± 1.81) mmHg vs.(12.57 ± 1.43) mmHg,(9.56 ± 1.32) mmHg vs.(11.23 ± 2.26) mmHg] (P ＜ 0.05),but there were no significant changes among 24 h systolic blood pressure variation coefficient (24 h SCV),systolic blood pressure variation coefficient during the day (dSCV) and 24 h diastolic blood pressure variation coefficient (24 h DCV),diastolic blood pressure variation coefficient during the day (dDCV),nocturnal diastolic blood pressure variation coefficient (nDCV) (P ＞ 0.05).After 8 weeks of medication plus,24 h SSD,24 h SCV,dSSD,dSCV and 24 h DSD,24 hDCV,dDSD,dDCV,nDSD in group B were significandy decreased compared with before combination plus[(10.23 ± 4.72) mmHg vs.(15.27 ± 3.23) mmHg,0.083 ± 0.032 vs.0.106 ± 0.019,(10.85 ± 3.29) mmHg vs.(15.09 ± 3.21) mmHg,0.080 ± 0.028 vs.0.096 ± 0.025,(10.13 ± 2.43) mmHg vs.(13.37 ±3.13) mmHg,0.111 ±0.035 vs.0.136 ±0.032,(9.58 ±2.49) mmHg vs.(12.29 ±3.27) mmHg,0.112 ± 0.036 vs.0.123 ± 0.04 1,(9.46 ± 2.78) mmHg vs.(11.19 ± 4.26) mmHg] (P ＜ 0.05),but there were no significant changes among nSSD,nSCV and nDCV (P ＞ 0.05).After 8 weeks of medication plus,24 h SSD,24 h SCV and 24 h DSD,24 h DCV,dSSD,dDSD,dSCV and dDCV in group B were significantly lower than those in group A (P ＜ 0.05).The nSSD,nDSD,nSCV and nDCV between 2 groups had no significant difference (P ＞ 0.05).Conclusions Amlodipine double dose or amlodipine single dose combined with perindopril can all effectively reduce the 24 hours' systolic and diastolic blood pressure variability,and the combined treatment is better and worthy of further promotion in clinic.