小檗碱联合西洛他唑治疗下肢动脉硬化闭塞症的疗效及机制

Efficacy and mechanism of berberine combined with cilostazol in the treatment of lower extremity arteriosclerosis obliterans

目的观察小檗碱联合西洛他唑治疗下肢动脉硬化闭塞症(ASO)患者的临床疗效,并探讨其可能的机制。方法采取前瞻性随机对照研究方法,选取2015年5月至2017年5月江苏省中医院诊断明确的间歇性跛行期下肢ASO患者30例纳入研究,随机分为治疗组和对照组,每组15例。对照组接受西洛他唑口服(100 mg/次,2次/d)治疗,治疗组在对照组基础上加用小檗碱口服(0.3 g/次,3次/d),观察其临床疗效,同时在治疗前后检测患者血常规、肝肾功能情况,检测比较内皮祖细胞(EPCs)数量及基质细胞衍生因子1α(SDF-1α)、血管内皮生长因子(VEGF)、内皮型一氧化氮合酶(eNOS)、一氧化氮(NO)水平。结果经过8周治疗,两组治疗前后血常规、肝肾功能、血脂、血糖比较差异无统计学意义(P>0.05),但治疗组收缩压显著低于治疗前[(132.10±8.78)mm Hgvs(136.50±9.31)mm Hg,t=2.377,P=0.041];两组右侧踝/肱指数(ABI)均显著增高(P<0.05),但左侧ABI仅治疗组显著改善(0.73±0.13 vs 0.69±0.15,t=4.075,P=0.003);两组治疗后间歇性跛行距离较治疗前均延长(P<0.05),而治疗组间歇性跛行距离增加值大于对照组[(307.70±119.40)m vs(181.80±29.20)m,t=3.471,P=0.001];治疗后治疗组EPCs数量较治疗前显著增加(0.044±0.007 vs 0.018±0.004,t=12.490,P<0.01),而对照组治疗前后变化差异无统计学意义(P>0.05);两组患者治疗后SDF-1α、eNOS、NO水平均增高(P<0.05,P<0.01),且治疗组治疗后各因子水平均高于对照组(P<0.05);而VEGF水平两组治疗前后差异无统计学意义(P>0.05)。结论小檗碱联合西洛他唑治疗下肢ASO安全性高,具有良好疗效,其可能通过SDF-1α通路影响eNOS及NO的产生进一步导致EPCs数量增加以及功能改变达到治疗目的。

Objective To investigate the clinical efficacy of berberine combined with cilostazol in the treatment of lower extremity arteriosclerosis obliterans(ASO)and to explore its possible mechanism.Methods A prospective randomized controlled study was conducted.A total of 30 patients with lower extremities ASO in intermittent claudication stage diagnosed at Jiangsu Province Hospital of Chinese Medicine from May 2015 to May 2017 were selected and randomly divided into treatment group and control group(n=15,each).The control group was treated with cilostazol(0.3 g/time,3 times/d),while the treatment group was treated with berberine(100 mg/time,3 times/d)on the basis of the control group.The clinical efficacy was observed.Blood routine test,liver and kidney function,the number of endothelial progenitor cells(EPCs)and the levels of stromal cell-derived factor-1α(SDF-1α),vascular endothelial growth factor(VEGF),endothelial nitric oxide synthase(eNOS)and nitric oxide(NO)levels were detected before and after treatment.Results After 8 weeks of treatment,there was no significant difference in blood routine,liver and kidney function,blood lipid and blood glucose between the two groups before and after treatment(P>0.05).Systolic blood pressure in the treatment group was significantly lower than that before treatment[(132.10±8.78)mm Hg vs(136.50±9.31)mm Hg,t=2.377,P=0.041].The right ankle/brachial index(ABI)significartly increased in both groups(P<0.05),but the left ABI level was significantly improved only in the treatment group(0.73±0.13 vs 0.69±0.15,t=4.075,P=0.003).After treatment,the intermittent claudication distance of the two groups were increased(P<0.05),while the increase value of intermittent claudication distance in the treatment group was higher[(307.70±119.40)m vs(181.80±29.20)m,t=3.471,P=0.001].After treatment,the number of EPCs in the treatment group increased significantly(0.044±0.007 vs 0.018±0.004,t=12.490,P<0.01),but there was no significant difference in the control group(P>0.05).After treatment,the levels of SDF-1α,eNOS and NO in the two groups increased(P<0.05,P<0.01),and the levels of each factor in the treatment group were higher than those in the control group(P<0.05).There was no significant difference in VEGF level between the two groups before and after treatment(P>0.05).Conclusions Berberine combined with cilostazol is safe and effective in the treatment of lower extremity ASO.It may affect the production of eNOS and NO through SDF-1αpathway,and further lead to the increase of EPCs and functional changes.