本文選題：特發(fā)性膜性腎病 + 腎病綜合征�。� 參考：《濱州醫(yī)學(xué)院》2016年碩士論文

【摘要】：研究一:CYP3A5基因多態(tài)性對特發(fā)性膜性腎病患者他克莫司藥代動力學(xué)指標(biāo)的影響研究目的:觀察不同CYP3A5基因型的特發(fā)性膜性腎病(idiopathic membranous nephropathy,IMN)患者在給予潑尼松聯(lián)合他克莫司(tacrolimus,TAC)治療6月,達(dá)到目標(biāo)全血谷濃度時的用藥劑量,推斷不同基因型與他克莫司用藥劑量之間的關(guān)系,初步探索由基因型指導(dǎo)的他克莫司個體化治療模式。方法:所選病例均來自濱州醫(yī)學(xué)院附屬醫(yī)院腎內(nèi)科住院,臨床表現(xiàn)為腎病綜合征(nephrotic syndrome,NS),病理確診為特發(fā)性膜性腎病(Idiopathic Membranous Nephropathy,IMN )的患者 60 例,熒光染色原位雜交(fluorescence in situ hybridization,FISH)技術(shù)檢測CYP3A5基因型。依據(jù)基因型將患者分為AA、AG、GG3組。他克莫司的全血谷濃度(C0)應(yīng)用均相酶擴(kuò)大免疫分析法(EMIT)測定;比較3組患者用藥后8周、12周、16周、24周時他克莫司全血谷濃度C0、用藥劑量D、劑量-調(diào)整谷濃度C0/D。按照臨床療效分為完全緩解(CR),部分緩解(PR)和無效(NR) 3組,比較三組患者各訪視點的TAC藥代動力學(xué)指標(biāo)變化。結(jié)果:60例特發(fā)性膜性腎病患者CYP3A5基因多態(tài)性(6986AG)G的基因頻率為 53.33%,其中AA組 12 例(20%); 組 32 例(53.33%); GG 組 16 例(26.67%)。3組患者他克莫司用藥8周、12周、16周、24周后的用藥劑量(D)、劑量-調(diào)整谷濃度(C0/D)的差異有統(tǒng)計學(xué)意義(均p0.05)。AA組患者他克莫司用藥劑量(D)約為GG組的2～3倍,AG組約為GG組的1～2倍。治療24周AA組患者的緩解率顯著低于AG、GG組(16.67%比81.25%、16.67%比87.25%,均p0.001)。CR、PR組的Co以及C0/D值均較NR組高,且隨用藥時間延長而提高,但組間差異無統(tǒng)計學(xué)意義(p0.05)。結(jié)論:對于IMN患者,不同CYP3A56986AG達(dá)到目標(biāo)血藥濃度時用藥劑量不同,據(jù)此,可推斷不同基因型患者的初始用藥劑量,并結(jié)合TDM,具有一定的臨床實用價值。研究二:五酯膠囊對CYP3A5基因表達(dá)型特發(fā)性膜性腎病患者他克莫司藥代動力學(xué)指標(biāo)的影響研究目的:針對CYP3A5基因表達(dá)型的特發(fā)性膜性腎病(IMN)患者,聯(lián)合應(yīng)用五酯膠囊(WZC),觀察五酯膠囊對他克莫司藥代動力學(xué)的影響,并注意聯(lián)用后的穩(wěn)定性和安全性,初步推斷聯(lián)合用藥后他克莫司的用藥劑量。方法:濱州醫(yī)學(xué)院附屬醫(yī)院腎內(nèi)科住院的患者,經(jīng)腎穿刺病理活檢診斷為特發(fā)性膜性腎病(IMN),且FISH檢測CYP3A5基因分型均為CYP3A5基因表達(dá)型(即AA、AG),共68例,應(yīng)用隨機(jī)數(shù)字表進(jìn)行分組,分別為治療組(五酯膠囊聯(lián)合他克莫司膠囊)、對照組(單用他克莫司膠囊),每組均為34例,實驗組失訪2例,對照組失訪1例。對兩組患者治療開始8周、16周、24周時他克莫司用藥劑量D、全血谷濃度C0、劑量-調(diào)整谷濃度C0/D進(jìn)行比較,比較治療24周兩組患者的有效率和不良反應(yīng)發(fā)生率。結(jié)果:對于CYP3A5基因表達(dá)型特發(fā)性膜性腎病而言,治療開始8周、16周、24周的各訪視點上,兩組患者的C0無顯著差異(p0.05);組間比較:治療組的D較對照組顯著降低(p0.001),C0/D較對照組顯著升高(p0.001);兩組患者組內(nèi)比較時不同訪視點D、C0/D的差異無統(tǒng)計學(xué)意義(p0.05),治療組他克莫司的平均用藥劑量為(0.037±0.002)mg.kg-1.d-1,約為對照組平均用藥劑量的60%。治療24周,兩組患者的治療有效率以及不良反應(yīng)發(fā)生率的差異無統(tǒng)計學(xué)意義(p0.05),但治療組的有效率較對照組有所升高。結(jié)論:五酯膠囊可減少CYP3A598G基因表達(dá)型(AA、AG) IMN患者他克莫司的用藥劑量,作用安全、平穩(wěn),減輕了患者的經(jīng)濟(jì)負(fù)擔(dān),且不增加藥物相關(guān)毒副作用。
[Abstract]:Study 1: the effect of CYP3A5 gene polymorphism on the pharmacokinetic index of tacrolimus in patients with idiopathic membranous nephropathy. Objective: To observe the specific CYP3A5 genotype of idiopathic membranous nephropathy (idiopathic membranous nephropathy, IMN) in patients with prednisone combined with tacrolimus, TAC (tacrolimus, TAC) for June, to achieve the target whole blood Valley concentration. The relationship between the different genotypes and the dose of tacrolimus was deduced, and the individualized treatment model of tacrolimus guided by genotyping was preliminarily explored. Methods: the selected cases were all from the hospitalized nephrology in Affiliated Hospital of Binzhou Medical College, the clinical manifestation was nephrotic syndrome, NS, and the pathological diagnosis was idiopathic. 60 patients with Idiopathic Membranous Nephropathy (IMN) were detected by fluorescence staining in situ hybridization (fluorescence in situ hybridization, FISH) technique for the detection of CYP3A5 genotypes. At 8 weeks, 12 weeks, 16 weeks and 24 weeks, the total blood Valley concentration of tacrolimus was C0, the dosage of the drug was D, and the dose adjustment Valley concentration C0/D. was divided into complete remission (CR), partial remission (PR) and ineffective (NR) 3 groups according to the clinical effect. The changes of the TAC pharmacokinetics index of the three groups of patients were compared. Results: 60 cases of idiopathic membranous nephropathy patients CYP3A5 The gene frequency of gene polymorphism (6986AG) G was 53.33%, of which 12 cases (20%) in group AA, 32 cases (53.33%), 16 cases in group GG, 16 (26.67%) in group.3, for 8 weeks, 12 weeks, 16 weeks, and 24 weeks, and the difference in dose adjustment Valley concentration (C0/D) was statistically significant (P0.05) the dosage of tacrolimus (D) in group.AA patients (D) was about 2~3 times in group GG and 1~2 times in group AG. The remission rate of group AA for 24 weeks was significantly lower than that of AG, group GG (16.67% to 81.25%, 16.67% ratio 87.25%, p0.001).CR, PR group Co and C0/D were higher than that of NR group, and increased with the duration of drug use, but there was no statistical difference between the groups. Conclusion: for the patients, there is no statistical difference. Conclusion: for the patients, there is no statistical difference. Conclusion: for the patients, there is no statistical difference. Conclusion: the difference between the groups is not statistically significant. Conclusion: the difference between the groups is not statistically significant. Conclusion: for the patients, there is no statistical difference. Conclusion: the difference between the groups is not statistically significant. Conclusion: the difference between the groups is not statistically significant. Conclusion: for the patients, there is no statistical difference. Conclusion: the difference between the groups is not statistically significant. Conclusion: the difference between the groups is not statistically significant. Conclusion: for the patients, there is no statistical difference. Conclusion: the difference between the groups is not statistically significant. Conclusion: for the patients, there is no statistical difference. Conclusion: for patients, there is no statistical difference. Conclusion: The dosage of G is different when it reaches the target blood concentration. According to this, we can infer the initial dosage of different genotype patients and combine with TDM, it has certain clinical practical value. Study two: the effect of five ester capsule on the pharmacokinetic index of tacrolimus in patients with CYP3A5 gene expression type idiopathic membranous nephropathy: aim at the CYP3A5 gene The expression type of idiopathic membranous nephropathy (IMN) patients, combined with five ester capsule (WZC), observed the effect of five ester capsule on the pharmacokinetics of tacrolimus, and paid attention to the stability and safety after combined use. The dosage of tacrolimus after combined use was preliminarily deduced. Pathological biopsy was diagnosed as idiopathic membranous nephropathy (IMN), and the FISH genotyping of CYP3A5 was CYP3A5 gene expression type (AA, AG). A total of 68 cases were divided into the treatment group (five ester capsule combined with Tacrolimus Capsules), the control group (single Tacrolimus Capsules), 34 cases in each group, and 2 cases in the experimental group. The two groups of patients were treated for 1 cases. At 8 weeks, 16 weeks and 24 weeks, the dosage of tacrolimus was D, the whole blood Valley concentration was C0, the dose adjusted Valley concentration C0/D was compared, and the rates of efficiency and adverse reactions were compared for two groups of patients in the 24 weeks. Results: for the CYP3A5 gene expression type idiopathic membranous nephropathy, the treatment began for 8 weeks, 16 weeks, 24 There was no significant difference in C0 between the two groups of patients (P0.05). Compared with the control group, the D in the treatment group was significantly lower than that in the control group (p0.001), and C0/D was significantly higher than the control group (p0.001). The difference of view point D in the two group was not statistically significant (P0.05), and the average dosage of tacrolimus in the treatment group was (0.037 + 0.002). Mg.kg-1.d-1, the average dose of 60%. in the control group was about 24 weeks. There was no significant difference in the effective rate of treatment and the incidence of adverse reactions between the two groups (P0.05), but the effective rate of the treatment group was higher than that of the control group. Conclusion: five ester capsules can reduce the dosage of tacrolimus in the CYP3A598G gene expression type (AA, AG) IMN patients. The dosage is safe and stable, which reduces the economic burden of patients and does not increase the side effects of drugs.
【學(xué)位授予單位】：濱州醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R692

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