【摘要】：目的：系統(tǒng)評(píng)價(jià)糖皮質(zhì)激素聯(lián)合他克莫司治療成人狼瘡性腎炎的療效和安全性。 方法：利用計(jì)算機(jī)檢索Cochrane圖書館對(duì)照試驗(yàn)的中心資料庫、Pubmed數(shù)據(jù)庫、OVID數(shù)據(jù)庫、萬方數(shù)據(jù)庫、中文期刊全文數(shù)據(jù)庫自建庫至2013年12月關(guān)于他克莫司治療狼瘡性腎炎的前瞻性臨床研究（CCT）或隨機(jī)對(duì)照研究（RCT），并同時(shí)手工檢索論文中的參考文獻(xiàn)。英文檢索關(guān)鍵字："Tacrolimus/FK506,Lupus nephritis/LN/Lupusglomerulosclerosis,Randomized clinical trials"。中文檢索關(guān)鍵字：“普樂可復(fù)/他克莫司/FK506，系統(tǒng)性紅斑狼瘡/狼瘡性腎炎”。根據(jù)Jadad評(píng)分方法評(píng)價(jià)納入研究文獻(xiàn)的質(zhì)量。用RevMan5.1軟件對(duì)提取資料進(jìn)行Meta分析。 結(jié)果：共納入10篇隨機(jī)對(duì)照研究和1篇隊(duì)列研究，共504例病人，其中他克莫司組251人，，對(duì)照組中糖皮質(zhì)激素聯(lián)合環(huán)磷酰胺為218例，糖皮質(zhì)激素聯(lián)合安慰劑對(duì)照為35例。對(duì)納入文獻(xiàn)的安全性及有效性指標(biāo)分別應(yīng)用RevMan5.1軟件繪制倒漏斗圖，結(jié)果顯示倒漏斗圖散點(diǎn)分布大致左右對(duì)稱，提示可能存在較小的發(fā)表偏倚。分析提取數(shù)據(jù)顯示,TAC組獲得部分緩解的平均時(shí)間較環(huán)磷酰胺更短，差異有統(tǒng)計(jì)學(xué)意義[MD=-1.05,95%CI(-1.61,-0.49),P=0.0002]。1、療效方面：(1)誘導(dǎo)治療6個(gè)月后根據(jù)是否為IV型狼瘡性腎炎進(jìn)行亞組分析，TAC組IV型LN的完全緩解率[OR=2.23，95%CI（1.08,4.63），P=0.03]顯著高于CTX組，但有效率（P=0.05）、尿蛋白下降水平（P=0.20）、血清白蛋白改善程度（P=0.72）及系統(tǒng)性紅斑狼瘡活動(dòng)指數(shù)（P=0.09）與對(duì)照組相比無顯著性差異。對(duì)其他病理類型亞組進(jìn)行分析顯示完全緩解率、有效率、尿蛋白下降水平、血清白蛋白改善情況和系統(tǒng)性紅斑狼瘡活動(dòng)性指數(shù)均顯著優(yōu)于對(duì)照組（P0.001）。（2）治療達(dá)3個(gè)月時(shí)TAC組的療效顯著優(yōu)于對(duì)照組（P0.05）。2、安全性方面：（1）TAC組肝損傷（P=0.03）、白細(xì)胞下降（P=0.0005）、月經(jīng)紊亂發(fā)生率（P=0.0002）顯著低于對(duì)照組。感染、胃腸道不適、腎毒性、血壓升高發(fā)生率與對(duì)照組相比無統(tǒng)計(jì)學(xué)差異（P0.05）。(2)TAC糖耐量異常的發(fā)生率顯著高于對(duì)照組（包含安慰劑組和環(huán)磷酰胺組）（P=0.01）,亞組分析顯示TAC組糖耐量異常發(fā)生率較CTX組相似（P=0.05）。 結(jié)論：1.他克莫司可迅速、有效地改善系統(tǒng)性紅斑狼瘡的全身癥狀，降低各種病理類型狼瘡性腎炎患者的尿蛋白、升高血清白蛋白，誘導(dǎo)治療3個(gè)月時(shí)有效率可達(dá)81.48%。2.他克莫司可有效提高各種病理類型的臨床緩解率，特別是非IV型或復(fù)合型狼瘡性腎炎患者的臨床緩解率。3.他克莫司的糖耐量異常發(fā)生率高于對(duì)照組，肝毒性、腎毒性、生殖毒性、血壓升高、胃腸道不良反應(yīng)、感染、白細(xì)胞下降的副作用與對(duì)照組相似或低于對(duì)照組，提示臨床應(yīng)用安全性良好。
[Abstract]:Objective: to evaluate the efficacy and safety of glucocorticoid combined with tacrolimus in the treatment of adult lupus nephritis. Methods: the central database of Cochrane library was searched by computer. A prospective clinical study of tacrolimus in the treatment of lupus nephritis (CCT) or a randomized controlled study (RCT),) was established from the full text database of Chinese journals until December 2013. Tacrolimus / FK506 Lupus nephritis / LN / Lupus conglomerulosclerosissis / Randomized clinical trials. Keywords: Procor / tacrolimus / FK506, systemic lupus erythematosus / lupus nephritis. The quality of the literature included in the study was evaluated according to the Jadad scoring method. The extracted data were analyzed by Meta with RevMan5.1 software. Results: a total of 504 patients were enrolled in 10 randomized controlled trials and 1 cohort study. Among them, 251 were tacrolimus group, 218 were glucocorticoid combined with cyclophosphamide and 35 were glucocorticoid plus placebo control group. The RevMan5.1 software was used to draw the inverted funnel graph for the safety and effectiveness indexes of the literature. The results showed that the distribution of the scattered points of the inverted funnel graph was approximately symmetrical to the left and right, suggesting that there might be a small publication bias. The average time of partial remission in TAC group was shorter than that in cyclophosphamide group. The difference was statistically significant [MD-1.0595 CI (-1.61U -0.49) Pu 0.0002] .1.Therapeutic effect: (1) after 6 months of induction therapy, the complete remission rate of type IV LN in TAC group [OR2.2395CI (1.084.63)] was significantly higher than that in CTX group, (1) after 6 months of induction therapy, the complete remission rate of type IV LN in TAC group was significantly higher than that in CTX group. But there were no significant differences in effective rate (P0. 05), urinary protein level (P0. 20), serum albumin improvement (P0. 72) and systemic lupus erythematosus activity index (P0. 09) compared with the control group. The analysis of other pathological subgroups showed complete remission rate, effective rate, and decreased level of urinary protein. The improvement of serum albumin and the activity index of systemic lupus erythematosus were significantly better than those of the control group (P0. 001). (2) for 3 months. The safety of TAC group was significantly better than that of the control group (P0.05). The safety aspects were as follows: (1) liver injury (P0. 03) and leukopenia (P0. 0005) in TAC group. The incidence of menstrual disorder (P0. 0002) was significantly lower than that in the control group. Infection, gastrointestinal discomfort, nephrotoxicity, There was no significant difference in the incidence of elevated blood pressure between the two groups (P0.05). (2). The incidence of abnormal glucose tolerance in TAC group was significantly higher than that in control group (P0. 01). The incidence of abnormal glucose tolerance in TAC group was similar to that in CTX group (P0. 01). Conclusion 1. Tacrolimus can rapidly and effectively improve systemic lupus erythematosus symptoms, reduce urine protein of patients with various pathological types of lupus nephritis, increase serum albumin, and the effective rate of induction therapy for 3 months can reach 81.48.2. Tacrolimus can effectively improve the clinical remission rate of various pathological types, especially in patients with non-IV or complex lupus nephritis. The incidence of impaired glucose tolerance in tacrolimus was higher than that in the control group, and the side effects of hepatotoxicity, nephrotoxicity, reproductive toxicity, elevated blood pressure, gastrointestinal adverse reactions, infection and leukopenia were similar or lower than those in the control group. It suggests that the clinical application 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】：2014
【分類號(hào)】：R593.242

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 楊岫巖,蔡小燕;紅斑狼瘡的誘導(dǎo)緩解與維持治療[J];廣東醫(yī)學(xué);2004年09期

2 李鑫;楊蕊;臧強(qiáng);胡永秀;;糖皮質(zhì)激素的藥理作用機(jī)制研究進(jìn)展[J];國際藥學(xué)研究雜志;2009年01期

3 張衍仕;陳成邦;鄧云;付乃雄;;他克莫司與環(huán)磷酰胺治療狼瘡性腎炎的臨床比較[J];廣西醫(yī)學(xué);2011年05期

4 黃金沐;池慧瓊;張忠陽;;他克莫司的研究概況[J];海峽藥學(xué);2010年11期

5 吳曉嬋;羅福漳;;他克莫司與環(huán)磷酰胺治療彌漫增殖性狼瘡腎炎的療效比較[J];吉林醫(yī)學(xué);2012年15期

6 王金鎧;張金巧;常英軍;孟建波;宋曉寧;孫麗霞;王俊祥;呂鴻雁;張運(yùn)清;李同健;吳薇薇;楊清云;;外周造血干細(xì)胞移植治療自身免疫性疾病療效隨訪[J];內(nèi)科急危重癥雜志;2005年05期

7 陳華;張文;;糖皮質(zhì)激素在系統(tǒng)性紅斑狼瘡治療中的應(yīng)用[J];內(nèi)科理論與實(shí)踐;2008年03期

8 邱敏麗;金歐;方霖楷;古潔若;;小劑量利妥昔單抗在治療系統(tǒng)性紅斑狼瘡中的作用分析[J];中外醫(yī)療;2013年25期

9 陳強(qiáng),劉志紅,胡偉新,姚小丹,陳惠萍,陳欣,程震,張波,曾彩虹,黎磊石;普樂可復(fù)治療Ⅳ型狼瘡性腎炎的前瞻性臨床研究[J];腎臟病與透析腎移植雜志;2002年04期

10 季大璽,龔德華,任冰,徐斌,劉蕓,張一丹,謝紅浪,陶靜,胡偉新,劉志紅,黎磊石;免疫吸附的臨床應(yīng)用及療效[J];腎臟病與透析腎移植雜志;2004年05期

本文編號(hào)：2180814