辣椒素对自发性高血压大鼠血管平滑肌细胞增殖和迁移的影响

Effect of Capsaicin on Proliferation and Migration of Vascular Smooth Muscle Cells in Spontaneously Hypertensive Rats

关键词:  辣椒素  厄贝沙坦  自发性高血压  血管平滑肌细胞  增殖  迁移

Key words:  capsaicin  irbesartan  spontaneous hypertension  vascular smooth muscle cells  proliferation  migration

摘要:

目的 探讨辣椒素对自发性高血压大鼠血管平滑肌细胞（vascular smooth muscle cells，VSMCs）增殖和迁移的影响。方法 体外构建自发性高血压大鼠血管平滑肌细胞系，分别采用20 μmol·L^-1辣椒素（高剂量组）、10 μmol·L^-1辣椒素（中剂量组）、5 μmol·L^-1辣椒素（低剂量组）和1 μmol·L^-1厄贝沙坦（厄贝沙坦组）直接处理细胞或特异性阻断CD36的表达后，再分别用20 μmol·L^-1辣椒素（高剂量组）、10 μmol·L^-1辣椒素（中剂量组）、5 μmol·L^-1辣椒素（低剂量组）和1 μmol·L^-1厄贝沙坦（厄贝沙坦组）处理细胞，采用MTT法检测VSMCs增殖情况，Boyden趋化小室检测VSMCs迁移情况，实时荧光定量PCR（qRT-PCR）和蛋白免疫印迹（Western blotting）检测平滑肌22a蛋白（smooth muscle 22a，SM22a）和调宁蛋白（Calponin）mRNA和蛋白的表达水平。结果 辣椒素和厄贝沙坦分别处理VSMCs后，与对照组相比，高、中、低剂量辣椒素组和厄贝沙坦组细胞增殖率和迁移率均有所降低，SM22a和Calponin的表达上调；与厄贝沙坦组相比，高剂量辣椒素组SM22a和Calponin的表达有所上调，中、低剂量辣椒素组SM22a和Calponin的表达均有所下调。特异性阻断CD36的表达后，与对照组相比，高、中、低剂量辣椒素组和厄贝沙坦组细胞增殖率降低，迁移率进一步降低，SM22a和Calponin表达上调；与厄贝沙坦组相比，高、中、低剂量辣椒素组SM22a的表达均有所上调，高、中、低剂量辣椒素组Calponin的表达有所下调。结论 高、中、低剂量辣椒素能够通过上调SM22a和Calponin的表达，抑制CD36的表达，来促进自发性高血压大鼠VSMCs由未分化表型向分化表型转化，从而抑制VSMCs的增殖及迁移和高血压血管重构的发生，促进其动脉管壁恢复正常的生理功能，有助于降低血压。

Abstract:

OBJECTIVE To investigate the effect of capsaicin on proliferation and migration of vascular smooth muscle cells(VSMCs) in spontaneously hypertensive rats. METHODS After construction of spontaneously hypertensive rats vascular smooth muscle cells in vitro, cells were treated with 20 μmol·L^-1 capsaicin(high dose group), 10 μmol·L^-1 capsaicin(middle dose group), 5 μmol·L^-1 capsaicin(low dose group), or 1 μmol·L^-1 irbesartan(irbesartan group) directly or treated with 20 μmol·L^-1 capsaicin(high dose group), 10 μmol·L^-1 capsaicin(middle dose group), 5 μmol·L^-1 capsaicin(low dose group), or 1 μmol·L^-1 irbesartan(irbesartan group) after specifically inhibiting the expression of CD36, the proliferation of VSMCs was detected by MTT method, the migration of VSMCs was detected by Boyden chemotaxis, and the changes of smooth muscle 22a (SM22a) and Calopnin mRNA and protein expression levels were detected by qRT-PCR and Western blotting. RESULTS After VSMCs were treated with capsaicin or irbesartan respectively, compared with the control group, the cell proliferation rate and migration rate in the high, middle, low dose of capsaicin group or irbesartan group reduced, SM22a and Calponin expression were up-regulated. Compared with the irbesartan group, SM22a and Calponine expression in the high dose of capsaicin group was up-regulated, while that in the middle or low dose of capsaicin group were down-regulated. After inhibiting CD36 expression specifically, compared with the control group, the cell proliferation rate in high, middle, low dose of capsaicin group or irbesartan group reduced, the migration rate was further reduced, and SM22a or Calponin expression were up-regulated. Compared with the irbesartan group, the SM22a expression in the high, middle, low dose of capsaicin group was up-regulated, while Calponin expression in the high, middle, low dose of capsaicin group were down-regulated. CONCLUSION High, middle, low dose of capsaicin can up-regulate SM22a and Calponin expression, inhibit the expression of CD36 to promote VSMCs in spontaneously hypertensive rats transform from undifferentiated phenotype to differentiation phenotype, thereby inhibiting proliferation and migration of VSMCs and vascular remodeling in hypertension, promoting restoration of arterial wall normal physiological function and to reduce blood pressure.