不同剂量阿托伐他汀在冠心病患者治疗早期抗炎机制的研究

发布时间：2018-08-31 10:15

【摘要】：实验目的:探讨阿托伐他汀在冠状动脉粥样硬化性心脏病(Coronary heart disease,CHD)患者中治疗早期的抗炎机制,同时评价不同剂量阿托伐他汀抗炎的临床效果。实验方法:纳入自2016年1月至2016年12月就诊吉林大学第二医院心血管内科,首次行冠状动脉造影术,确诊为CHD,但未达到植入支架标准且既往无口服他汀类药物史患者(74例)。将其随机分组为:对照组(20例)、A组(27例)、B组(27例)。实验对象在常规治疗基础上,对照组给予20mg/天阿托伐他汀钙片睡前口服;A组实验对象给予40mg/天阿托伐他汀钙片睡前口服;B组实验对象给予60mg/天阿托伐他汀钙片睡前口服。入院时收集实验对象的一般资料:年龄、性别、吸烟比例、饮酒比例、体重指数(Body Mass Index,BMI)、高血压比例、收缩压(Systolic blood pressure,SBP)及舒张压(Diastolic blood pressure,DBP)、心率、白细胞(White blood cell,WBC)、血小板(Platelet,PLT)、尿酸(Uric acid,UA)、同型半胱氨酸(Homocysteine,Hcy)。于治疗前即入院当天(D1)、治疗后即入院后第3天(D3)及入院后第7天(D7)分别进行血红素氧合酶-1(Heme oxygenase-1,HO-1)、超敏C反应蛋白(Highly sensitive C-reactive protein,hs-CRP)及肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)测定。于D1、D7分别进行甘油三酯(Triglycerides,TG)、总胆固醇(Total cholesterol,TC)、低密度脂蛋白胆固醇(Low density lipoprotein-cholesterol,LDL-C)、高密度脂蛋白胆固醇(High density lipoprotein-cholesterol,HDL-C)、谷丙转氨酶(Alanine aminotransferase,ALT)、谷草转氨酶(Aspartate transaminase,AST)、血清肌酐及肌酸激酶(Creatine kinase,CK)检测。H0-1及TNF-α采用酶联免疫法测定。hs-CRP、TG、TC、LDL-C、HDL-C、ALT、AST、肌酐、CK采用全自动生化分析仪检测。所有数据进行统计学分析,结果以P0.05为差异有统计学意义。实验结果:一般资料结果:三组实验对象在年龄、性别、吸烟比例、饮酒比例、BMI、高血压比例、SBP、DBP、心率、WBC、PLT、UA、Hcy方面比较,差异均无统计学意义(P0.05)。血脂结果:三组D1的血脂结果比较,差异无统计学意义(P0.05)。三组D7与D1的血脂结果比较,仅B组TC及LDL-C在D7较D1下降,差异有统计学意义(P0.05);B组D7的TC及LDL-C与A组和对照组比较下降,差异有统计学意义(P0.05)。HO-1水平结果:三组D1的HO-1水平比较,差异无统计学意义(P0.05)。给予阿托伐他汀治疗后,A组HO-1水平在D3和D7明显高于对照组,差异有统计学意义(P0.05)。B组HO-1水平在D3和D7明显高于A组及对照组,差异有统计学意义(P0.05)。随着给药时间推移,对照组的HO-1表达水平差异无统计学意义(P0.05);而A组和B组HO-1表达水平逐渐增加,即A组和B组分别在D1、D3、D7时HO-1水平差异有统计学意义(P0.05),为D1D3D7。hs-CRP及TNF-α水平结果:三组D1的hs-CRP及TNF-α水平比较,差异无统计学意义(P0.05)。给予阿托伐他汀治疗后,A组hs-CRP及TNF-α水平在D3和D7明显低于对照组,差异有统计学意义(P0.05);B组hs-CRP及TNF-α水平在D3和D7明显低于A组及对照组,差异有统计学意义(P0.05)。随着给药时间推移,对照组的hs-CRP及TNF-α表达水平差异无统计学意义(P0.05);而A组和B组的hs-CRP及TNF-α表达水平逐渐降低,即在D1、D3、D7时的hs-CRP及TNF-α水平差异有统计学意义(P0.05),为D1D3D7。HO-1与hs-CRP及TNF-α相关性分析:A组及B组54例患者在D1与治疗后(D3与D7)的HO-1水平与炎症因子hs-CRP及TNF-α水平采用pearson线性相关性分析结果显示:HO-1水平与hs-CRP及TNF-α水平呈负相关,差异有统计学意义(r1=-0.373,r2=-0.401,P0.01);进行线性回归分析结果显示:HO-1表达水平上升,hs-CRP及TNF-α水平降低。差异有统计学意义(P0.01)。阿托伐他汀安全性:三组D1的ALT、AST、肌酐、CK结果比较,差异均无统计学意义(P0.05);每组D7的ALT、AST、肌酐、CK指标较D1比较,差异均无统计学意义(P0.05)。实验结论:1.CHD患者中,早期强化阿托伐他汀能够有效降低TC和LDL-C水平。2.在阿托伐他汀CHD治疗早期,HO-1与hs-CRP及TNF-α呈负相关,可能是通过诱导HO-1表达上调,抑制hs-CRP和TNF-α的水平。3.CHD患者中,早期应用大剂量阿托伐他汀能够降低炎症因子hs-CRP和TNF-α水平,且随着剂量的增加,hs-CRP和TNF-α水平越低。4.在CHD患者中,早期强化他汀治疗无不良反应,有较好的安全性。
[Abstract]:OBJECTIVE: To investigate the anti-inflammatory mechanism of atorvastatin in the treatment of coronary heart disease (CHD), and to evaluate the clinical efficacy of different doses of atorvastatin in the treatment of CHD. CHD was diagnosed by coronary angiography, but it did not meet the standard of stent implantation and had no history of oral statins (74 cases). The patients were randomly divided into control group (20 cases), group A (27 cases) and group B (27 cases). Patients in group B were given 60 mg/day of atorvastatin calcium tablets before bedtime. General data were collected at admission: age, sex, smoking, alcohol consumption, body mass index (BMI), hypertension, systolic blood pressure (SBP) and diastolic blood pressure (Diastolic b). Blood pressure, DBP, heart rate, white blood cell (WBC), platelet (PLT), uric acid (UA), homocysteine (Hcy). Heme oxygenase-1 (HO-1) and hypersensitive C-reactive eggs were administered on the first day of admission (D1), the third day (D3) and the seventh day (D7) after admission, respectively. Highly sensitive C-reactive protein (hs-CRP) and tumor necrosis factor-alpha (TNF-alpha) were measured. Triglycerides (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C) were measured at D1 and D7, respectively. H-density lipoprotein-cholesterol, HDL-C, Alanine aminotransferase (ALT), Aspartate transaminase (AST), creatine kinase (CK), serum creatinine and creatine kinase (CK) were detected. H0-1 and TNF-a were determined by enzyme-linked immunoassay. hs-CRP, TG, TC, LDL-C, HDL-C, ALT, AST, CK, using automatic biochemical analyzer. Results: General data: There were no significant differences in age, sex, smoking, drinking, BMI, hypertension, SBP, DBP, heart rate, WBC, PLT, UA, Hcy among the three groups (P There was no significant difference in serum lipids (P 0.05). Compared with D7 and D1, TC and LDL-C in group B decreased significantly (P 0.05), while TC and LDL-C in group B decreased significantly (P 0.05) compared with group A and control group (P 0.05). After treatment with atorvastatin, the level of HO-1 in group A was significantly higher in D3 and D7 than that in control group (P 0.05). The level of HO-1 in group B was significantly higher in D3 and D7 than that in group A and control group (P 0.05). The levels of HO-1 in group A and group B were significantly higher than those in group D1, D3 and D7 (P 0.05). The results showed that the levels of hs-CRP and TNF-alpha in group A were significantly lower than those in group D1 (P 0.05). After atorvastatin treatment, the levels of hs-CRP and TNF-alpha in group A were significantly lower than those in group D3 and D7 (P 0.05). The levels of hs-CRP and TNF-alpha in group B were significantly lower than those in group A and control group at D3 and D7 (P 0.05). There were significant differences in the levels of hs-CRP and TNF-alpha at D1, D3 and D7 (P 0.05). The correlation analysis of D1D3D7.HO-1 with hs-CRP and TNF-alpha showed that the levels of HO-1 and hs-CRP and TNF-alpha in 54 patients in group A and B were significantly higher than those in group B after D1 and treatment (D3 and D7). There was a significant negative correlation (r1 = - 0.373, R2 = - 0.401, P 0.01); linear regression analysis showed that the expression of HO-1 increased, while the levels of hs-CRP and TNF-alpha decreased. The difference was statistically significant (P 0.01). Atorvastatin safety: The results of ALT, AST, creatinine and CK in D 1 of the three groups were not statistically significant (P 0.05); ALT, A and CK in D7 of each group were not statistically significant (P 0.05). There was no significant difference in ST, creatinine and CK between CHD patients and D1 patients (P 0.05). Conclusion: 1. Early intensive atorvastatin can effectively reduce the levels of TC and LDL-C. 2. In the early period of atorvastatin treatment, HO-1 was negatively correlated with hs-CRP and TNF-alpha, possibly by inducing the up-regulation of HO-1 expression and inhibiting the levels of hs-CRP and TNF-alpha. High-dose atorvastatin can reduce the levels of inflammatory cytokines hs-CRP and TNF-alpha in patients with CHD, and the levels of hs-CRP and TNF-alpha are lower with the increase of dosage. 4. In patients with CHD, early intensive statin therapy has no adverse reactions and is safe.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.4

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