中国组织工程研究与临床康复
中國組織工程研究與臨床康複
중국조직공정연구여림상강복
JOURNAL OF CLINICAL REHABILITATIVE TISSUE ENGINEERING RESEARCH
2009年
53期
10443-10451
,共9页
余少杰%彭龙开%谢续标%彭风华%王彧%蓝恭斌
餘少傑%彭龍開%謝續標%彭風華%王彧%藍恭斌
여소걸%팽룡개%사속표%팽풍화%왕욱%람공빈
人类白细胞抗原%肾移植%糖尿病%移植后糖尿病%钙调神经蛋白抑制药物
人類白細胞抗原%腎移植%糖尿病%移植後糖尿病%鈣調神經蛋白抑製藥物
인류백세포항원%신이식%당뇨병%이식후당뇨병%개조신경단백억제약물
背景:移植后糖尿病也具有2型糖尿病的高度遗传异质性的特点,湘赣地区汉族人群人类白细胞抗原(HLA)与移植后糖尿病相关性研究领域尚属空白.目的:分析湘赣地区肾移植患者HLA与移植后糖尿病的相关性,确定该地区人群移植后糖尿病的易感基因和保护基因,并为肾移植后个体化用药提供参考数据. 设计、时间及地点:调查分析,于2007-05/2008-07在中南大学湘雅二医院泌外器官移植科完成.对象:收集中南大学湘雅二医院泌外器官移植科2003/2008接受肾移植患者的个人信息资料、移植前后各项检查结果、配型资料等,并进行随访登记.共收集得符合条件的患者共195例,其中移植后糖尿病患者22例,非移植后糖尿病移植受者173例.方法:使用χ~2检验对移植后糖尿病组与非移植后糖尿病组患者各HLA抗原的出现频率进行比较分析;根据移植后使用的钙调神经蛋白抑制药物类药物不同将195例患者分成环孢素A组和他克莫司组,通过χ~2检验对这两组患者移植后糖尿病的发生率进行比较;根据患者年龄,将其分为高龄组(≥ 40岁)和非高龄组(< 40岁),通过χ~2检验对这两组患者移植后糖尿病的发病率进行比较.主要观察指标:所有患者定期随访,随访项目为年龄、血压、尿量、血尿常规、肝肾功能、血糖及血药浓度.结果:HLA-A30和HLA-DR7可能是湘赣地区汉族人群移植后糖尿病的易感基因,未发现对移植后糖尿病具有明显保护作用的基因.在使用小剂量、低血药浓度钙调神经蛋白抑制药物类药物预防排斥反应情况下,环孢素A组患者和他克莫司组患者移植后糖尿病的发病率差异无显著性意义(P > 0.05);高龄移植受者移植后糖尿病的发生率显著高于低龄移植受者(P < 0.05).结论:HLA-A30和HLA-DR7可能是湖南和江西部分地区汉族人群移植后糖尿病的易感基因,对于携带这两种基因的移植受者,有必要在移植后密切监测血糖、尿糖,适时调整免疫抑制药物的种类和用量;在小剂量低浓度的使用原则下,他克莫司并不明显增加移植后糖尿病的发生率;高龄患者移植后糖尿病发生率显著增加,加之高龄患者本身已有的基础性心脑血管疾病的发病率升高,罹患移植后糖尿病更易导致心脑血管事件的发生,因此,对高龄移植受者进行常规的血糖和尿糖的监测和控制,并建立个体化的免疫抑制方案就显得更为重要.
揹景:移植後糖尿病也具有2型糖尿病的高度遺傳異質性的特點,湘贛地區漢族人群人類白細胞抗原(HLA)與移植後糖尿病相關性研究領域尚屬空白.目的:分析湘贛地區腎移植患者HLA與移植後糖尿病的相關性,確定該地區人群移植後糖尿病的易感基因和保護基因,併為腎移植後箇體化用藥提供參攷數據. 設計、時間及地點:調查分析,于2007-05/2008-07在中南大學湘雅二醫院泌外器官移植科完成.對象:收集中南大學湘雅二醫院泌外器官移植科2003/2008接受腎移植患者的箇人信息資料、移植前後各項檢查結果、配型資料等,併進行隨訪登記.共收集得符閤條件的患者共195例,其中移植後糖尿病患者22例,非移植後糖尿病移植受者173例.方法:使用χ~2檢驗對移植後糖尿病組與非移植後糖尿病組患者各HLA抗原的齣現頻率進行比較分析;根據移植後使用的鈣調神經蛋白抑製藥物類藥物不同將195例患者分成環孢素A組和他剋莫司組,通過χ~2檢驗對這兩組患者移植後糖尿病的髮生率進行比較;根據患者年齡,將其分為高齡組(≥ 40歲)和非高齡組(< 40歲),通過χ~2檢驗對這兩組患者移植後糖尿病的髮病率進行比較.主要觀察指標:所有患者定期隨訪,隨訪項目為年齡、血壓、尿量、血尿常規、肝腎功能、血糖及血藥濃度.結果:HLA-A30和HLA-DR7可能是湘贛地區漢族人群移植後糖尿病的易感基因,未髮現對移植後糖尿病具有明顯保護作用的基因.在使用小劑量、低血藥濃度鈣調神經蛋白抑製藥物類藥物預防排斥反應情況下,環孢素A組患者和他剋莫司組患者移植後糖尿病的髮病率差異無顯著性意義(P > 0.05);高齡移植受者移植後糖尿病的髮生率顯著高于低齡移植受者(P < 0.05).結論:HLA-A30和HLA-DR7可能是湖南和江西部分地區漢族人群移植後糖尿病的易感基因,對于攜帶這兩種基因的移植受者,有必要在移植後密切鑑測血糖、尿糖,適時調整免疫抑製藥物的種類和用量;在小劑量低濃度的使用原則下,他剋莫司併不明顯增加移植後糖尿病的髮生率;高齡患者移植後糖尿病髮生率顯著增加,加之高齡患者本身已有的基礎性心腦血管疾病的髮病率升高,罹患移植後糖尿病更易導緻心腦血管事件的髮生,因此,對高齡移植受者進行常規的血糖和尿糖的鑑測和控製,併建立箇體化的免疫抑製方案就顯得更為重要.
배경:이식후당뇨병야구유2형당뇨병적고도유전이질성적특점,상공지구한족인군인류백세포항원(HLA)여이식후당뇨병상관성연구영역상속공백.목적:분석상공지구신이식환자HLA여이식후당뇨병적상관성,학정해지구인군이식후당뇨병적역감기인화보호기인,병위신이식후개체화용약제공삼고수거. 설계、시간급지점:조사분석,우2007-05/2008-07재중남대학상아이의원비외기관이식과완성.대상:수집중남대학상아이의원비외기관이식과2003/2008접수신이식환자적개인신식자료、이식전후각항검사결과、배형자료등,병진행수방등기.공수집득부합조건적환자공195례,기중이식후당뇨병환자22례,비이식후당뇨병이식수자173례.방법:사용χ~2검험대이식후당뇨병조여비이식후당뇨병조환자각HLA항원적출현빈솔진행비교분석;근거이식후사용적개조신경단백억제약물류약물불동장195례환자분성배포소A조화타극막사조,통과χ~2검험대저량조환자이식후당뇨병적발생솔진행비교;근거환자년령,장기분위고령조(≥ 40세)화비고령조(< 40세),통과χ~2검험대저량조환자이식후당뇨병적발병솔진행비교.주요관찰지표:소유환자정기수방,수방항목위년령、혈압、뇨량、혈뇨상규、간신공능、혈당급혈약농도.결과:HLA-A30화HLA-DR7가능시상공지구한족인군이식후당뇨병적역감기인,미발현대이식후당뇨병구유명현보호작용적기인.재사용소제량、저혈약농도개조신경단백억제약물류약물예방배척반응정황하,배포소A조환자화타극막사조환자이식후당뇨병적발병솔차이무현저성의의(P > 0.05);고령이식수자이식후당뇨병적발생솔현저고우저령이식수자(P < 0.05).결론:HLA-A30화HLA-DR7가능시호남화강서부분지구한족인군이식후당뇨병적역감기인,대우휴대저량충기인적이식수자,유필요재이식후밀절감측혈당、뇨당,괄시조정면역억제약물적충류화용량;재소제량저농도적사용원칙하,타극막사병불명현증가이식후당뇨병적발생솔;고령환자이식후당뇨병발생솔현저증가,가지고령환자본신이유적기출성심뇌혈관질병적발병솔승고,리환이식후당뇨병경역도치심뇌혈관사건적발생,인차,대고령이식수자진행상규적혈당화뇨당적감측화공제,병건립개체화적면역억제방안취현득경위중요.
BACKGROUND: Post-transplantation diabetes mellitus has the same characteristics as type II diabetes mellitus; however, correlation between human leucocyte antigen (HLA) and post-transplantation diabetes mellitus remains unclear among Han population in Hunan and Jiangxi provinces. OBJECTIVE: To analyze the correlation between HLA and post-transplantation diabetes mellitus, to determine predisposing genes and protecting genes of post-transplantation diabetes mellitus, and to provide reference data for personalized medicine of post-transplantation diabetes mellitus. DESIGN, TIME AND SETTING: A survey analysis was performed at Department of Urological Organ Transplantation, the Second Xiangya Hospital of Central South University from May 2007 to July 2008. PARTICIPANTS: Patients with kidney transplantation selected from Department of Urological Organ Transplantation, the Second Xiangya Hospital of Central South University between 2003 and 2008 were followed-up on individual information, testing results before and after transplantation, and zygosity. Among 195 included cases, there were 22 patients with post-transplantation diabetes mellitus and 173 with non-post-transplantation diabetes mellitus. Methods: METHODS: χ~2 was used to compare frequency of HLA antigen between post-transplantation diabetes mellitus and non-post-transplantation diabetes mellitus groups. The 195 patients were divided into ciclosporin A group and tacrolimus group according to immunosuppressive regimen, and the incidence of post-transplantation diabetes mellitus were compared usingχ~2 test. All the patients were then divided into elderly group (age ≥ 40) and low-age group (age < 40), and the incidences of post-transplantation diabetes mellitus were calculated and compared usingχ~2 test.MAIN OUTCOME MEASURES: Following-up was performed including age, blood pressure, urine volume, blood and urine routine test, liver and kidney function, blood glucose, and blood drug level. RESULTS: HLA-A30 and HLA-DR7 might be the predisposing genes of post-transplantation diabetes mellitus in south China; however, protecting genes were not found. Low dosage and low blood drug level of calcineurin inhibitors were applied in this study, and there was no significant difference in the incidence of post-transplantation diabetes mellitus between ciclosporin A and tacrolimus groups (P > 0.05). The incidence of post-transplantation diabetes mellitus in elderly group was significantly higher than that in low-age group (P < 0.05).CONCLUSION: HLA-A30 and HLA-DR7 might be the predisposing genes of post-transplantation diabetes mellitus in south China; therefore, they should be paid much attention on levels of blood glucose and urine glucose after transplantation so as to adjust the types and dosages of immunosuppressive drug in time. Low-dosage and low-concentration tacrolimus was not increased incidence of post-transplantation diabetes mellitus remarkably. However, the incidence of post-transplantation diabetes mellitus in the elderly patients was high; moreover, the incidence of cardio-cerebrovascular disease was also high. Therefore, post-transplantation diabetes mellitus might easily cause the onset of cardio-cerebrovascular disease. It was important for elderly patients to monitor blood glucose and urine glucose levels and set up an individual immunosuppression program following transplantation.