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慢性腎衰竭與血漿胃泌素胃動素的相關性分析

2014-08-08 09:55劉永明許翠萍
中國當代醫藥 2014年14期
關鍵詞:胃泌素慢性腎衰竭相關性

劉永明+許翠萍

[摘要] 目的 探討慢性腎衰竭與血漿胃泌素、胃動素的相關性。 方法 選擇本院2013年1~12月收治的90例慢性腎衰竭患者與9例正常健康者,以腎小球濾過率分組并與血漿胃泌素、胃動素進行相關性統計分析。 結果 慢性腎衰竭組測定的血漿胃泌素、胃動素的指標均高于對照組;慢性腎衰竭五組的胃泌素與對照組比較差異有統計學意義(P<0.01);除GFR3、GFR4組胃動素與對照組比較差異有統計學意義(P<0.01),其余3組胃動素均差異無統計學意義(P>0.05);GFR1、GFR2、GFR3、GFR4、GFR5組及對照組的GFR與胃泌素呈正相關;GFR1、GFR2、GFR5組及對照組的GFR與胃動素呈正相關,GFR3、GFR4組的GFR與胃動素呈負相關。 結論 腎臟損害可能會導致胃泌素和胃動素的升高,但是并不能證明胃泌素和胃動素的升高就是腎臟損害的嚴重征兆,胃泌素和胃動素是消化道疾病的測定指標,可以衡量消化系統功能的損害程度,雖然它們的分泌與腎臟損害有一定程度的相關性,但不能單純用胃泌素與胃動素的測定指標來衡量腎臟實質的損傷。

[關鍵詞] 慢性腎衰竭;胃泌素;胃動素;相關性;指標

[中圖分類號] R692.5[文獻標識碼] A[文章編號] 1674-4721(2014)05(b)-0032-05

Correlation analysis of gastrin and motilin of plasma with chronic renal failure

LIU Yong-Ming1 XU Cui-Ping2▲

1.Shanxi Medical University,Taiyuan 030001,China;2.Department of Gastroenterology,Shanxi Medical University,the First Clinical Hospital,Taiyuan 030001,China

[Abstract] Objective To investigate the correlation analysis of gastrin and motilin of plasma with chronic renal failure. Methods 90 cases of chronic renal failure patients and 9 normal healthy were selected in our hospital from January 2013 to December 2013,they were grouped by glomerular filtration rate,and the test parameters of gastrin and motilin of plasma were correlation statistical analyzed. Results The indicators of gastrin and motilin in chronic renal failure group were higher than those of the control group,the gastrin in five chronic renal failure group compared with the control group,the difference was statistically significant (P<0.01),the motilin:except GFR3,GFR4 group compared with control group,the difference was statistically significant (P<0.01),the rest of the three groups,the difference was no statistically significant (P>0.05).The GFR were positively associated with gastrin in GFR1,GFR2,GFR3,GFR4,GFR5 groups and control group.The GFR were positively associated with motilin in GFR1,GFR2,GFR5 groups and control group,but there were negatively associated with motilin in GFR3,GFR4 groups. Conclusion Kidney damage may ead to elevated gastrin and motilin,but does not prove that the rise of gastrin and motilin is kidney damage serious symptom,but does not prove that the rise of gastrin and motilin is the kidney damage serious symptom,gastrin and motilin is the determination of the digestive tract disease indexes,to measure the digestive system function damage degree,although they secrete has a certain degree of correlation with kidney damage,but you can′t simply use gastrin and motilin measurement indicators to measure renal parenchymal damage.

[Key words] Chronic renal failure;Gastrin;Motilin;Relevance;Index

慢性腎衰竭(chronic renal failure,CRF)是一種常見的臨床綜合征,可以由各種原因引起的腎臟損害,是一種進行性惡化、腎實質不可逆轉的損傷,也是各種腎臟疾病進展的終末結局[1-3]。目前,臨床以消化道為首發癥狀的CRF患者日漸增多,胃泌素(GAS)、胃動素(MOT)是消化道疾病的常見檢測指標,而腎臟又是GAS、MOT滅活和消除的主要場所,它們是一種連鎖反應關系[4-5],目前臨床對CRF的研究報道較多,但是對于CRF患者血漿GAS、MOT測定的相關性分析報道較少,本研究通過回顧本院一年來收治的CRF患者的血漿GAS、MOT變化水平并行相關性分析,以探討慢性腎衰竭與血漿GAS、MOT的相關性。

1 資料與方法

1.1 一般資料

選取本院2013年1~12月末本院收治的90例以消化道為首發癥狀的CRF的患者(非透析)與9例正常健康者作為研究對象,90例CRF患者均未透析,病史1~4年,平均(2.04±0.63)年;其中男性56例,女性34例;年齡36~71歲,平均(44.16±2.32)歲;原發性疾?。郝阅I小球腎炎33例,慢性腎盂腎炎14例,慢性間質性腎炎13例,腎病綜合征8例,高血壓腎病17例,紫癜性腎炎1例,腎髓質囊性病2例,遺傳性腎炎1例,尿毒癥性海綿腎1例。9例正常健康者,男性6例,女性3例,年齡31~58歲,平均(39.05±0.10)歲,均無肝腎及內分泌疾病,未服用任何藥物。

1.2 分組方法

以臨床入院時所查腎小球濾過率(glomerular filtration rate,GFR)為標準劃分,GFR≥90 ml/min為GFR1組;60 ml/min≤GFR<90 ml/min為GFR2組;30 ml/min ≤GFR<60 ml/min為GFR3組;15 ml/min≤GFR<30 ml/min為GFR4組;GFR<15 ml/min為GFR5組;正常健康者為對照組。

1.3 檢測方法

受檢者均于清晨空腹采血2 ml,注入預先準備的試管中,搖勻后,以3000 r/min離心10 min,取血漿作GAS、MOT酶聯免疫法的測定,陰性、陽性對照,1 h孵育后,進行洗板,加相應底物,避光0.5 h進行反應,加終止液完成反應進程,讀取數值。試劑盒選用上海撫生生物科技發展有限公司生產的試劑盒(CAS:FS2011)。

1.4 統計學處理

所得數據采用SPSS 17.0軟件進行統計學處理,計量資料采用均數±標準差表示,采用t檢驗,關系測定采用相關回歸分析法,以P<0.05為差異有統計學意義。

2 結果

2.1 不同GFR分組與對照組患者GAS 、MOT的比較

CRF組的血漿GAS、MOT均高于對照組;CRF中5組與對照組的GAS差異有統計學意義(P<0.01);除了GFR3、GFR4組的MOT與對照組比較差異有統計學意義(P<0.01),其余3組均差異無統計學意義(P>0.05)(表1)。

表1 不同GFR分組與對照組GAS 、MOT的比較(pg/ml,x±s)

與對照組比較,*P<0.01

2.2 各組GFR與血漿GAS、MOT的相關性

GFR1組的GAS、MOT均與GFR呈正相關(圖1);GFR2組的GAS、MOT均與GFR呈正相關(圖2);GFR3組的GAS與GFR呈正相關,MOT與GFR呈負相關(圖3);GFR4組的GAS與GFR呈正相關,MOT與GFR呈負相關(圖4);GFR5組的GAS、MOT均與GFR呈正相關(圖5)。

圖1 GFR≥90 ml/min腺素的相關性分析

3 討論

對于CRF的患者來說,消化系統癥狀是最早和最突出的表現,由于體內大量代謝產物的堆積,酸堿平衡失調,電解質紊亂,都會引起不同程度的消化道癥狀,胃腸道癥狀主要原因為胃腸道排尿素增多,經尿素酶分解產生氨刺激胃腸道黏膜引起,此外,也與胃腸道多肽激素代謝障礙引起的黏膜屏障機制紊亂和胃腸道轉移性鈣化因素有關[6-8]。

GAS和MOT為胃腸多肽激素,MOT主要由空腸的EC細胞分泌,分子量約為2700,具有調節胃動力和胃排空的作用;GAS主要由胃竇G細胞分泌,分子量約為2000,具有促進胃酸分泌的作用[9]。由于腎臟是GAS、MOT代謝和排泄的主要場所,當腎功能受損時,血清GAS和MOT可在機體內蓄積,導致高GAS血癥和高MOT血癥而引起不同程度的消化道癥狀[10-12]。

本研究結果顯示,CRF患者的血漿GAS、MOT的指標均高于正常對照組,且與對照組差異有統計學意義;有文獻報道[13],隨著病情加重,MOT和GAS升高更明顯,但本研究通過血漿GAS及MOT的測定比較發現,并非隨著病情的嚴重程度,MOT和GAS一定會升高。而不同分期的CRF患者由于病情輕重不一,個體差異不同,表現的消化道癥狀程度也并非完全一致,所以測定的GAS和MOT數值也不一定是隨著病情的嚴重程度而升高。本研究結果顯示,CRF中5組與對照組的GAS差異有統計學意義;除了GFR3、GFR4組的MOT與對照組比較差異有統計學意義,其余3組均差異無統計學意義,說明存在個體差異。本研究結果顯示,GFR1組的GAS、MOT均與GFR呈正相關;GFR2組的GAS、MOT均與GFR呈正相關;GFR3組的GAS與GFR呈正相關;GFR4組的GAS與GFR呈正相關,GFR5組的GAS、MOT均與GFR呈正相關,說明隨著腎臟損害嚴重程度的增加,GAS隨之不斷升高;GFR3、GFR4組MOT與GFR呈負相關,其余組別呈正相關,可能GFR3、GFR4組患者的腎臟損害較輕,消化道癥狀不明顯或者個體腎臟功能修復,EC細胞分泌MOT不足所致。

從基礎理論上分析,本研究中CRF患者的GAS和MOT明顯高于正常人,且大部分患者的GAS和MOT均與GFR呈正相關。其原因可能為:①大多數CRF患者有惡心、嘔吐、腹瀉、腹脹等腸道反應,而導致迷走神經興奮、張力增高,所以會引起GAS和MOT升高;②腎衰竭時,腎臟損害嚴重,可使GAS和MOT的排泄減少,體內蓄積,導致GAS和MOT明顯升高;③CRF患者常有胃酸分泌功能降低,這種低酸度反映了胃液中不斷增多的氨而引起的中和作用或由于胃黏膜屏障功能的喪失而引起的胃炎,導致氫離子逆彌散入黏膜內所致,胃酸過低可能會刺激GAS釋放,血清GAS含量增高[14-16]。腎臟損害可能會導致GAS和MOT升高,但是并不能證明GAS和MOT的升高就是腎臟損害的嚴重征兆。

總之,CRF是一種臨床常見的多發病,可累及多個系統,臨床表現多樣性,部分患者起病隱匿,尤其早期缺少特征性的臨床表現,易出現誤診和漏診[17-19]。大多數CRF患者以消化道為首發癥狀就診,GAS和MOT是消化道疾病的檢測指標,可以衡量消化系統功能的損害程度[20],雖然它們的分泌與腎臟損害有一定程度的相關性,但不能單純用GAS與MOT來衡量腎臟實質的損傷,因為患者個體存在差異,腎臟實質有一定損害時,GAS和MOT的水平未必會反映現實,因此延誤診治而導致病情惡化。

[參考文獻]

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[7]Freedman BI,Hicks PJ,Bostrom MA,et al.Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9)are strongly associated with end-stage renal disease historically attributed to hypertension in African Americans[J].Kidney Int,2009,75(1):736-745.

[8]Genovese G,Friedman DJ,Ross MD,et al.Association of trypanolytic ApoL1 variants with kidney disease in African Americans[J].Science,2010,13,(329):841-845.

[9]Furgala A,Blauk-Kadzielska U,Stojakowska M,et al.Gasttic dysfunction in dialysed patients with chronic renal failure[J].Folia Med Cracov,2012,52(1):39-55.

[10]Donadio C.Effect of glomerular filtration rate impairment on diagnostic performance of neutrophil gelatinase-associated lipocalin and B-type natriuretic peptide as markers of acute cardiac and renal failure in chronic kidney disease patients[J].Crit Care,2014,18(1):39.

[11]Meijers BK,Van Kerckhoven S,Verbeke K,et al.The uremic retention solute p-cresyl sulfate and markers of endothelial damage[J].Am J Kidney Dis,2009,54(1):891-901.

[12]Lin CJ,Wu CJ,Pan CF,et al.Serum protein-bound uraemic toxins and clinical outcomes in haemodialysis patients[J].Nephrol Dial Transplant,2010;25(1):3693-3700.

[13]Harmar AJ.Clinical endocrinology and metabolism. Receptors for gut peptides[J].Clin Endocrinol Metab,2004, 18(4):463-475.

[14]Lin CJ,Pan CF,Chuang CK,et al.Gastrointestinal-related uremic toxins in peritoneal dialysis: a pilot study with a 5-year follow-up[J].Arch Med Res,2013,44(7):535-541.

[15]Lin CJ,Pan CF,Liu HL,et al.The role of protein-bound uremic toxins on peripheral artery disease and vascular access failure in patients on hemodialysis[J].Atherosclerosis,2012,225(1):173-179.

[16]Lin CJ,Liu HL,Pan CF,et al.Indoxyl sulfate predicts cardiovascular disease and renal function deterioration in advanced chronic kidney disease[J].Arch Med Res,2012, 43(1):451-456.

[17]Kobori H,Nangaku M,Navar GL,et al.The Intrarenal Renin-Angiotensin System: from physiology to the pathobiology of hypertension and kidney disease[J].Pharmacol Rev, 2007,59(3):251-287.

[18]José M López-Novoa,Ana B Rodríguez-Pe?觡a,Alberto Ortiz,et al.Etiopathology of chronic tubular,glomerular and renovascular nephropathies:clinical implications[J].J Transl Med,2011,9(1):13.

[19]Bellomo G,Venanzi S,Verdura C,et al.Association of uric acid with change in kidney function in healthy normotensive individuals[J].Am J Kidney Dis,2010,56(1):264-272.

[20]Zeisberg M,Duffield JS.Resolved:EMT produces fibroblasts in the kidney[J].J Am Soc Nephrol,2010,21(1):1247-1253.

(收稿日期:2014-03-17本文編輯:林利利)

[作者簡介] 劉永明(1980-),男,碩士,主管技師,研究方向:消化內科

▲通訊作者:許翠萍,女,教授

[5]Sirinek KR,Odorisio TM,Gaskill HV,et al.Chronic renal failure:effect of hemodialysis on gastrointestinal hormones[J].Am J Surg,1984,148(6):732-735.

[6]Kao WH,Klag MJ,Meoni LA,et al.Family Investigation of Nephropathy and Diabetes Research Group. MYH9 is associated with nondiabetic end-stage renal disease in African Americans[J].Nat Genet,2008,40(1):1185-1192.

[7]Freedman BI,Hicks PJ,Bostrom MA,et al.Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9)are strongly associated with end-stage renal disease historically attributed to hypertension in African Americans[J].Kidney Int,2009,75(1):736-745.

[8]Genovese G,Friedman DJ,Ross MD,et al.Association of trypanolytic ApoL1 variants with kidney disease in African Americans[J].Science,2010,13,(329):841-845.

[9]Furgala A,Blauk-Kadzielska U,Stojakowska M,et al.Gasttic dysfunction in dialysed patients with chronic renal failure[J].Folia Med Cracov,2012,52(1):39-55.

[10]Donadio C.Effect of glomerular filtration rate impairment on diagnostic performance of neutrophil gelatinase-associated lipocalin and B-type natriuretic peptide as markers of acute cardiac and renal failure in chronic kidney disease patients[J].Crit Care,2014,18(1):39.

[11]Meijers BK,Van Kerckhoven S,Verbeke K,et al.The uremic retention solute p-cresyl sulfate and markers of endothelial damage[J].Am J Kidney Dis,2009,54(1):891-901.

[12]Lin CJ,Wu CJ,Pan CF,et al.Serum protein-bound uraemic toxins and clinical outcomes in haemodialysis patients[J].Nephrol Dial Transplant,2010;25(1):3693-3700.

[13]Harmar AJ.Clinical endocrinology and metabolism. Receptors for gut peptides[J].Clin Endocrinol Metab,2004, 18(4):463-475.

[14]Lin CJ,Pan CF,Chuang CK,et al.Gastrointestinal-related uremic toxins in peritoneal dialysis: a pilot study with a 5-year follow-up[J].Arch Med Res,2013,44(7):535-541.

[15]Lin CJ,Pan CF,Liu HL,et al.The role of protein-bound uremic toxins on peripheral artery disease and vascular access failure in patients on hemodialysis[J].Atherosclerosis,2012,225(1):173-179.

[16]Lin CJ,Liu HL,Pan CF,et al.Indoxyl sulfate predicts cardiovascular disease and renal function deterioration in advanced chronic kidney disease[J].Arch Med Res,2012, 43(1):451-456.

[17]Kobori H,Nangaku M,Navar GL,et al.The Intrarenal Renin-Angiotensin System: from physiology to the pathobiology of hypertension and kidney disease[J].Pharmacol Rev, 2007,59(3):251-287.

[18]José M López-Novoa,Ana B Rodríguez-Pe?觡a,Alberto Ortiz,et al.Etiopathology of chronic tubular,glomerular and renovascular nephropathies:clinical implications[J].J Transl Med,2011,9(1):13.

[19]Bellomo G,Venanzi S,Verdura C,et al.Association of uric acid with change in kidney function in healthy normotensive individuals[J].Am J Kidney Dis,2010,56(1):264-272.

[20]Zeisberg M,Duffield JS.Resolved:EMT produces fibroblasts in the kidney[J].J Am Soc Nephrol,2010,21(1):1247-1253.

(收稿日期:2014-03-17本文編輯:林利利)

[作者簡介] 劉永明(1980-),男,碩士,主管技師,研究方向:消化內科

▲通訊作者:許翠萍,女,教授

[5]Sirinek KR,Odorisio TM,Gaskill HV,et al.Chronic renal failure:effect of hemodialysis on gastrointestinal hormones[J].Am J Surg,1984,148(6):732-735.

[6]Kao WH,Klag MJ,Meoni LA,et al.Family Investigation of Nephropathy and Diabetes Research Group. MYH9 is associated with nondiabetic end-stage renal disease in African Americans[J].Nat Genet,2008,40(1):1185-1192.

[7]Freedman BI,Hicks PJ,Bostrom MA,et al.Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9)are strongly associated with end-stage renal disease historically attributed to hypertension in African Americans[J].Kidney Int,2009,75(1):736-745.

[8]Genovese G,Friedman DJ,Ross MD,et al.Association of trypanolytic ApoL1 variants with kidney disease in African Americans[J].Science,2010,13,(329):841-845.

[9]Furgala A,Blauk-Kadzielska U,Stojakowska M,et al.Gasttic dysfunction in dialysed patients with chronic renal failure[J].Folia Med Cracov,2012,52(1):39-55.

[10]Donadio C.Effect of glomerular filtration rate impairment on diagnostic performance of neutrophil gelatinase-associated lipocalin and B-type natriuretic peptide as markers of acute cardiac and renal failure in chronic kidney disease patients[J].Crit Care,2014,18(1):39.

[11]Meijers BK,Van Kerckhoven S,Verbeke K,et al.The uremic retention solute p-cresyl sulfate and markers of endothelial damage[J].Am J Kidney Dis,2009,54(1):891-901.

[12]Lin CJ,Wu CJ,Pan CF,et al.Serum protein-bound uraemic toxins and clinical outcomes in haemodialysis patients[J].Nephrol Dial Transplant,2010;25(1):3693-3700.

[13]Harmar AJ.Clinical endocrinology and metabolism. Receptors for gut peptides[J].Clin Endocrinol Metab,2004, 18(4):463-475.

[14]Lin CJ,Pan CF,Chuang CK,et al.Gastrointestinal-related uremic toxins in peritoneal dialysis: a pilot study with a 5-year follow-up[J].Arch Med Res,2013,44(7):535-541.

[15]Lin CJ,Pan CF,Liu HL,et al.The role of protein-bound uremic toxins on peripheral artery disease and vascular access failure in patients on hemodialysis[J].Atherosclerosis,2012,225(1):173-179.

[16]Lin CJ,Liu HL,Pan CF,et al.Indoxyl sulfate predicts cardiovascular disease and renal function deterioration in advanced chronic kidney disease[J].Arch Med Res,2012, 43(1):451-456.

[17]Kobori H,Nangaku M,Navar GL,et al.The Intrarenal Renin-Angiotensin System: from physiology to the pathobiology of hypertension and kidney disease[J].Pharmacol Rev, 2007,59(3):251-287.

[18]José M López-Novoa,Ana B Rodríguez-Pe?觡a,Alberto Ortiz,et al.Etiopathology of chronic tubular,glomerular and renovascular nephropathies:clinical implications[J].J Transl Med,2011,9(1):13.

[19]Bellomo G,Venanzi S,Verdura C,et al.Association of uric acid with change in kidney function in healthy normotensive individuals[J].Am J Kidney Dis,2010,56(1):264-272.

[20]Zeisberg M,Duffield JS.Resolved:EMT produces fibroblasts in the kidney[J].J Am Soc Nephrol,2010,21(1):1247-1253.

(收稿日期:2014-03-17本文編輯:林利利)

[作者簡介] 劉永明(1980-),男,碩士,主管技師,研究方向:消化內科

▲通訊作者:許翠萍,女,教授

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