【摘要】：實(shí)驗(yàn)?zāi)康?探討阿托伐他汀在冠狀動(dòng)脈粥樣硬化性心臟病(Coronary heart disease,CHD)患者中治療早期的抗炎機(jī)制,同時(shí)評(píng)價(jià)不同劑量阿托伐他汀抗炎的臨床效果。實(shí)驗(yàn)方法:納入自2016年1月至2016年12月就診吉林大學(xué)第二醫(yī)院心血管內(nèi)科,首次行冠狀動(dòng)脈造影術(shù),確診為CHD,但未達(dá)到植入支架標(biāo)準(zhǔn)且既往無口服他汀類藥物史患者(74例)。將其隨機(jī)分組為:對(duì)照組(20例)、A組(27例)、B組(27例)。實(shí)驗(yàn)對(duì)象在常規(guī)治療基礎(chǔ)上,對(duì)照組給予20mg/天阿托伐他汀鈣片睡前口服;A組實(shí)驗(yàn)對(duì)象給予40mg/天阿托伐他汀鈣片睡前口服;B組實(shí)驗(yàn)對(duì)象給予60mg/天阿托伐他汀鈣片睡前口服。入院時(shí)收集實(shí)驗(yàn)對(duì)象的一般資料:年齡、性別、吸煙比例、飲酒比例、體重指數(shù)(Body Mass Index,BMI)、高血壓比例、收縮壓(Systolic blood pressure,SBP)及舒張壓(Diastolic blood pressure,DBP)、心率、白細(xì)胞(White blood cell,WBC)、血小板(Platelet,PLT)、尿酸(Uric acid,UA)、同型半胱氨酸(Homocysteine,Hcy)。于治療前即入院當(dāng)天(D1)、治療后即入院后第3天(D3)及入院后第7天(D7)分別進(jìn)行血紅素氧合酶-1(Heme oxygenase-1,HO-1)、超敏C反應(yīng)蛋白(Highly sensitive C-reactive protein,hs-CRP)及腫瘤壞死因子-α(Tumor necrosis factor-α,TNF-α)測(cè)定。于D1、D7分別進(jìn)行甘油三酯(Triglycerides,TG)、總膽固醇(Total cholesterol,TC)、低密度脂蛋白膽固醇(Low density lipoprotein-cholesterol,LDL-C)、高密度脂蛋白膽固醇(High density lipoprotein-cholesterol,HDL-C)、谷丙轉(zhuǎn)氨酶(Alanine aminotransferase,ALT)、谷草轉(zhuǎn)氨酶(Aspartate transaminase,AST)、血清肌酐及肌酸激酶(Creatine kinase,CK)檢測(cè)。H0-1及TNF-α采用酶聯(lián)免疫法測(cè)定。hs-CRP、TG、TC、LDL-C、HDL-C、ALT、AST、肌酐、CK采用全自動(dòng)生化分析儀檢測(cè)。所有數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析,結(jié)果以P0.05為差異有統(tǒng)計(jì)學(xué)意義。實(shí)驗(yàn)結(jié)果:一般資料結(jié)果:三組實(shí)驗(yàn)對(duì)象在年齡、性別、吸煙比例、飲酒比例、BMI、高血壓比例、SBP、DBP、心率、WBC、PLT、UA、Hcy方面比較,差異均無統(tǒng)計(jì)學(xué)意義(P0.05)。血脂結(jié)果:三組D1的血脂結(jié)果比較,差異無統(tǒng)計(jì)學(xué)意義(P0.05)。三組D7與D1的血脂結(jié)果比較,僅B組TC及LDL-C在D7較D1下降,差異有統(tǒng)計(jì)學(xué)意義(P0.05);B組D7的TC及LDL-C與A組和對(duì)照組比較下降,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。HO-1水平結(jié)果:三組D1的HO-1水平比較,差異無統(tǒng)計(jì)學(xué)意義(P0.05)。給予阿托伐他汀治療后,A組HO-1水平在D3和D7明顯高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。B組HO-1水平在D3和D7明顯高于A組及對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。隨著給藥時(shí)間推移,對(duì)照組的HO-1表達(dá)水平差異無統(tǒng)計(jì)學(xué)意義(P0.05);而A組和B組HO-1表達(dá)水平逐漸增加,即A組和B組分別在D1、D3、D7時(shí)HO-1水平差異有統(tǒng)計(jì)學(xué)意義(P0.05),為D1D3D7。hs-CRP及TNF-α水平結(jié)果:三組D1的hs-CRP及TNF-α水平比較,差異無統(tǒng)計(jì)學(xué)意義(P0.05)。給予阿托伐他汀治療后,A組hs-CRP及TNF-α水平在D3和D7明顯低于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05);B組hs-CRP及TNF-α水平在D3和D7明顯低于A組及對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。隨著給藥時(shí)間推移,對(duì)照組的hs-CRP及TNF-α表達(dá)水平差異無統(tǒng)計(jì)學(xué)意義(P0.05);而A組和B組的hs-CRP及TNF-α表達(dá)水平逐漸降低,即在D1、D3、D7時(shí)的hs-CRP及TNF-α水平差異有統(tǒng)計(jì)學(xué)意義(P0.05),為D1D3D7。HO-1與hs-CRP及TNF-α相關(guān)性分析:A組及B組54例患者在D1與治療后(D3與D7)的HO-1水平與炎癥因子hs-CRP及TNF-α水平采用pearson線性相關(guān)性分析結(jié)果顯示:HO-1水平與hs-CRP及TNF-α水平呈負(fù)相關(guān),差異有統(tǒng)計(jì)學(xué)意義(r1=-0.373,r2=-0.401,P0.01);進(jìn)行線性回歸分析結(jié)果顯示:HO-1表達(dá)水平上升,hs-CRP及TNF-α水平降低。差異有統(tǒng)計(jì)學(xué)意義(P0.01)。阿托伐他汀安全性:三組D1的ALT、AST、肌酐、CK結(jié)果比較,差異均無統(tǒng)計(jì)學(xué)意義(P0.05);每組D7的ALT、AST、肌酐、CK指標(biāo)較D1比較,差異均無統(tǒng)計(jì)學(xué)意義(P0.05)。實(shí)驗(yàn)結(jié)論:1.CHD患者中,早期強(qiáng)化阿托伐他汀能夠有效降低TC和LDL-C水平。2.在阿托伐他汀CHD治療早期,HO-1與hs-CRP及TNF-α呈負(fù)相關(guān),可能是通過誘導(dǎo)HO-1表達(dá)上調(diào),抑制hs-CRP和TNF-α的水平。3.CHD患者中,早期應(yīng)用大劑量阿托伐他汀能夠降低炎癥因子hs-CRP和TNF-α水平,且隨著劑量的增加,hs-CRP和TNF-α水平越低。4.在CHD患者中,早期強(qiáng)化他汀治療無不良反應(yīng),有較好的安全性。
[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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R541.4

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