中国全科医学
中國全科醫學
중국전과의학
CHINESE GENERAL PRACTICE
2014年
21期
2462-2466
,共5页
陈琰%高依依%李占园%叶菡洋%郑育%周志宏
陳琰%高依依%李佔園%葉菡洋%鄭育%週誌宏
진염%고의의%리점완%협함양%정육%주지굉
成纤维细胞生长因子21%肾功能不全,慢性%模型,动物
成纖維細胞生長因子21%腎功能不全,慢性%模型,動物
성섬유세포생장인자21%신공능불전,만성%모형,동물
Fibroblastgrowthfactor21%Renalinsufficiency,chronic%Models,animal
目的：观察慢性肾脏病（CKD）患者和CKD动物模型中成纤维细胞生长因子21（FGF21）的表达及其与肾功能等因素的相关性，以探讨FGF21在CKD进展中的意义。方法临床研究：选取2012年在温州医科大学附属第二医院就诊的CKD患者200例，根据估算肾小球滤过率（eGFR）将患者分为CKD1～2期组（76例）、 CKD3～4期组（56例）和CKD5期组（68例）；另选取本院同期体检健康者40例（对照组）。检测所有受检者一般资料及外周血空腹血糖、空腹胰岛素、血脂、清蛋白、肌酐、尿素氮、尿酸、脂联素和FGF21水平。实验研究：取清洁级雄性8周龄C57BL/6小鼠36只，将其随机分为正常对照组（ C组）、模型组（ M组）、低剂量FGF21干预组（ M＋L组）和高剂量FGF21干预组（ M＋H组），每组9只，观察小鼠给药期间的生存状况，4周后处死小鼠，检测小鼠血清肌酐、尿素氮、尿酸、清蛋白水平，观察肾组织病理改变，并采用免疫组化方法检测肾组织中FGF21的表达情况。结果临床研究结果：对照组、 CKD1～2期组、 CKD3～4期组、 CKD5期组血清FGF21水平〔（147.3±12.2）、（402.9±35.0）、（845.8±238.7）、（1447.9±146.5） ng/L〕依次增加（P＜0.05）。 CKD患者中，合并糖尿病者血清FGF21水平高于非糖尿病者〔（1253.0±170.1） ng/L与（714.0±82.1） ng/L， P＜0.05〕。通过对年龄、性别、 BMI、糖尿病校正后， Pearson相关分析显示血清FGF21水平与三酰甘油、血肌酐、尿素氮、脂联素呈正相关（ P＜0.05），与低密度脂蛋白、高密度脂蛋白、 eGFR呈负相关（ P＜0.05）。实验研究结果： M组小鼠血肌酐、尿素氮、血尿酸水平较C组升高；与M组比较， FGF21干预后小鼠血肌酐、尿素氮、血尿酸水平升高，且M＋H组上述3项肾功能指标较M＋L组恶化（ P＜0.05）。光镜下肾组织病理显示M＋H组小鼠肾脏损伤较M＋L组加重；免疫组化检测显示， M组小鼠肾组织中FGF21表达较C组升高； FGF21干预后，随着FGF21干预剂量的增加，肾组织中FGF21表达亦升高。结论随着CKD病情的进展，患者血清FGF21水平逐渐升高。随着FGF21干预剂量的升高， CKD小鼠肾脏损伤加重。
目的：觀察慢性腎髒病（CKD）患者和CKD動物模型中成纖維細胞生長因子21（FGF21）的錶達及其與腎功能等因素的相關性，以探討FGF21在CKD進展中的意義。方法臨床研究：選取2012年在溫州醫科大學附屬第二醫院就診的CKD患者200例，根據估算腎小毬濾過率（eGFR）將患者分為CKD1～2期組（76例）、 CKD3～4期組（56例）和CKD5期組（68例）；另選取本院同期體檢健康者40例（對照組）。檢測所有受檢者一般資料及外週血空腹血糖、空腹胰島素、血脂、清蛋白、肌酐、尿素氮、尿痠、脂聯素和FGF21水平。實驗研究：取清潔級雄性8週齡C57BL/6小鼠36隻，將其隨機分為正常對照組（ C組）、模型組（ M組）、低劑量FGF21榦預組（ M＋L組）和高劑量FGF21榦預組（ M＋H組），每組9隻，觀察小鼠給藥期間的生存狀況，4週後處死小鼠，檢測小鼠血清肌酐、尿素氮、尿痠、清蛋白水平，觀察腎組織病理改變，併採用免疫組化方法檢測腎組織中FGF21的錶達情況。結果臨床研究結果：對照組、 CKD1～2期組、 CKD3～4期組、 CKD5期組血清FGF21水平〔（147.3±12.2）、（402.9±35.0）、（845.8±238.7）、（1447.9±146.5） ng/L〕依次增加（P＜0.05）。 CKD患者中，閤併糖尿病者血清FGF21水平高于非糖尿病者〔（1253.0±170.1） ng/L與（714.0±82.1） ng/L， P＜0.05〕。通過對年齡、性彆、 BMI、糖尿病校正後， Pearson相關分析顯示血清FGF21水平與三酰甘油、血肌酐、尿素氮、脂聯素呈正相關（ P＜0.05），與低密度脂蛋白、高密度脂蛋白、 eGFR呈負相關（ P＜0.05）。實驗研究結果： M組小鼠血肌酐、尿素氮、血尿痠水平較C組升高；與M組比較， FGF21榦預後小鼠血肌酐、尿素氮、血尿痠水平升高，且M＋H組上述3項腎功能指標較M＋L組噁化（ P＜0.05）。光鏡下腎組織病理顯示M＋H組小鼠腎髒損傷較M＋L組加重；免疫組化檢測顯示， M組小鼠腎組織中FGF21錶達較C組升高； FGF21榦預後，隨著FGF21榦預劑量的增加，腎組織中FGF21錶達亦升高。結論隨著CKD病情的進展，患者血清FGF21水平逐漸升高。隨著FGF21榦預劑量的升高， CKD小鼠腎髒損傷加重。
목적：관찰만성신장병（CKD）환자화CKD동물모형중성섬유세포생장인자21（FGF21）적표체급기여신공능등인소적상관성，이탐토FGF21재CKD진전중적의의。방법림상연구：선취2012년재온주의과대학부속제이의원취진적CKD환자200례，근거고산신소구려과솔（eGFR）장환자분위CKD1～2기조（76례）、 CKD3～4기조（56례）화CKD5기조（68례）；령선취본원동기체검건강자40례（대조조）。검측소유수검자일반자료급외주혈공복혈당、공복이도소、혈지、청단백、기항、뇨소담、뇨산、지련소화FGF21수평。실험연구：취청길급웅성8주령C57BL/6소서36지，장기수궤분위정상대조조（ C조）、모형조（ M조）、저제량FGF21간예조（ M＋L조）화고제량FGF21간예조（ M＋H조），매조9지，관찰소서급약기간적생존상황，4주후처사소서，검측소서혈청기항、뇨소담、뇨산、청단백수평，관찰신조직병리개변，병채용면역조화방법검측신조직중FGF21적표체정황。결과림상연구결과：대조조、 CKD1～2기조、 CKD3～4기조、 CKD5기조혈청FGF21수평〔（147.3±12.2）、（402.9±35.0）、（845.8±238.7）、（1447.9±146.5） ng/L〕의차증가（P＜0.05）。 CKD환자중，합병당뇨병자혈청FGF21수평고우비당뇨병자〔（1253.0±170.1） ng/L여（714.0±82.1） ng/L， P＜0.05〕。통과대년령、성별、 BMI、당뇨병교정후， Pearson상관분석현시혈청FGF21수평여삼선감유、혈기항、뇨소담、지련소정정상관（ P＜0.05），여저밀도지단백、고밀도지단백、 eGFR정부상관（ P＜0.05）。실험연구결과： M조소서혈기항、뇨소담、혈뇨산수평교C조승고；여M조비교， FGF21간예후소서혈기항、뇨소담、혈뇨산수평승고，차M＋H조상술3항신공능지표교M＋L조악화（ P＜0.05）。광경하신조직병리현시M＋H조소서신장손상교M＋L조가중；면역조화검측현시， M조소서신조직중FGF21표체교C조승고； FGF21간예후，수착FGF21간예제량적증가，신조직중FGF21표체역승고。결론수착CKD병정적진전，환자혈청FGF21수평축점승고。수착FGF21간예제량적승고， CKD소서신장손상가중。
ObjectiveTostudytheexpressionoffibroblastgrowthfactor21(FGF21)inpatientsandanimalmodel with chronic kidney disease (CKD), and the correlation between FGF21 and renal function, and to investigate the significance of FGF21 in the development of CKD .Methods The clinical study: a total of 200 patients with CKD in the Second Hospital Af-filiated to Wenzhou Medical University were selected , CKD patients were divided into three groups according to the eGFR: CKD1-2 group (76 cases), CKD3-4 group (56 cases) and CKD5 group (68 cases); Meanwhile, 40 healthy examinees in our hospital were selected as control group .General information , levels of peripheral blood fasting glucose , fasting insulin , blood lip-id, albumin, creatinine, uric acid, adiponectin and FGF21 of all examinees were detected.The experimental study: thirty six male C57BL/6 rats of clean grade at 8 weeks were randomly divided into four groups: control group (C group), model group (M group), low dose FGF21 group (M+L group) and high dose FGF21 group (M+H group), 9 in each group, living status of rats was observed during the administration period .Rats were sacrificed 4 weeks after surgery, levels of albumin, creatinine, uric acid and adiponectin were detected , pathological changes of renal tissue were observed , the expression of FGF21 in kidney tissue was detected by the immunohistochemistry .Results The results of clinical study: plasma FGF21 level in control group , ObjectiveTostudytheexpressionoffibroblastgrowthfactor21(FGF21)inpatientsandanimalmodel with chronic kidney disease (CKD), and the correlation between FGF21 and renal function, and to investigate the significance of FGF21 in the development of CKD .Methods The clinical study: a total of 200 patients with CKD in the Second Hospital Af-filiated to Wenzhou Medical University were selected , CKD patients were divided into three groups according to the eGFR: CKD1-2 group (76 cases), CKD3-4 group (56 cases) and CKD5 group (68 cases); Meanwhile, 40 healthy examinees in our hospital were selected as control group .General information , levels of peripheral blood fasting glucose , fasting insulin , blood lip-id, albumin, creatinine, uric acid, adiponectin and FGF21 of all examinees were detected.The experimental study: thirty six male C57BL/6 rats of clean grade at 8 weeks were randomly divided into four groups: control group (C group), model group (M group), low dose FGF21 group (M+L group) and high dose FGF21 group (M+H group), 9 in each group, living status of rats was observed during the administration period .Rats were sacrificed 4 weeks after surgery, levels of albumin, creatinine, uric acid and adiponectin were detected , pathological changes of renal tissue were observed , the expression of FGF21 in kidney tissue was detected by the immunohistochemistry .Results The results of clinical study: plasma FGF21 level in control group , CKD1-2 group, CKD3-4 group and CKD5 group 〔 (147.3 ±12.2), (402.9 ±35.0), (845.8 ±238.7), (1 447.9 ±146.5) ng/L〕 increased in an order (P<0.05) .Serum FGF-21 level in CKD patients with diabetes mellitus (DM) was significantly higher than that in CKD patients without DM 〔 (1 253.0 ±170.1) ng/L and (714.0 ±82.1) ng/L, P<0.05〕. After adjusting for age, gender, body mass index (BMI) and DM, results of Pearson correlation analysis indicated that serum FGF21 level was positively correlated with triacylglycerol , creatinine, urea nitrogen and adiponectin (P<0.05), and serum FGF21 level was negatively correlated with low density lipoprotein , high density lipoprotein and eGFR ( P<0.05) .The results of experimental study:levels of serum creatinine , urea nitrogen and blood uric acid in rats of M group were significantly higher than those in rats of C group .Levels of serum creatinine , urea nitrogen and serum uric acid in rats of FGF 21 group were signifi-cantly higher than those in rats of M group , the above 3 renal function indexes in M +H group were significantly worse than those in M+L group ( P<0.05) .Renal pathology examination under light microscope showed that renal injury of rats in M +H group was worse than that in M+L group.Immunohistochemical staining revealed that the expression level of FGF 21 in renal tissue of M group was higher than that in renal tissue of C group .The expression level of FGF21 in renal tissue increased with FGF21 interven-tion dose.Conclusion The serum FGF21 level of patients increases with the development of CKD .Renal injury of CKD rats gets worse with FGF21 intervention dose.
