中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2015年
40期
3313-3316
,共4页
翟丽敏%叶山东%顾俊菲%杨迪%胡闻
翟麗敏%葉山東%顧俊菲%楊迪%鬍聞
적려민%협산동%고준비%양적%호문
糖尿病,2型%二甲双胍%足细胞%格列本脲%足糖萼蛋白
糖尿病,2型%二甲雙胍%足細胞%格列本脲%足糖萼蛋白
당뇨병,2형%이갑쌍고%족세포%격렬본뇨%족당악단백
Diabetes mellitus%type 2%Metformin%Podocytes%Glyburide%Podocalyxin
目的 观察二甲双胍对2型糖尿病大鼠肾小球足细胞特异性蛋白podocalyxin (PCX)表达和排泄的影响,了解其对肾小球足细胞的保护作用.方法 高脂喂养结合腹腔注射小剂量链脲佐菌素建立大鼠2型糖尿病模型.25只造模成功的SD大鼠随机分为糖尿病组(9只) ,二甲双胍组(300 mg· kg-1· d-1,8只),格列本脲组(5 mg· kg-1 · d-1,8只);并设正常对照组(8 只).干预8周后,检测大鼠血糖(BG)、糖化血红蛋白(HbA1c)、尿PCX和尿肌酐的排泄;免疫组化观察大鼠肾脏PCX蛋白表达水平;实时定量PCR检测大鼠PCX mRNA表达水平;电镜下观察大鼠肾脏病理改变.结果 二甲双胍组、格列本脲组大鼠BG[(9.6 ±1.1)、(9.9 ±1.1)比 (15.6 ±1.6)mmol/L,均P<0.05]和HbA1c[(7.0 ±0.3)%、(8.0 ±1.0)%比(12.4 ±0.6)%,均P<0.05]均显著低于糖尿病组,但两药物干预组间差异均无统计学意义(均P>0.05).糖尿病组大鼠尿PCX肌酐比高于正常对照组[(697 ±136)比(94 ±25) ng/g,P<0.05],并伴有肾脏组织PCX蛋白(0.75 ±0.11 比3.18 ± 0.14,P<0.05)和mRNA(0.08 ±0.09比1.00 ±0.02,P<0.05)表达减少.二甲双胍和格列本脲治疗后上述指标均显著改善(均P<0.05),且二甲双胍组尿PCX肌酐比[(404 ±83)比(516 ±38) ng/g]、肾脏组织PCX蛋白(1.54 ±0.06比1.06 ±0.10)和mRNA(0.23 ±0.01比0.16 ±0.04)与格列本脲组比较差异均有统计学意义(均P<0.05).进一步观察发现,糖尿病组与正常对照组比较肾脏基底膜厚度[(267 ±22) 比(106 ±10) nm,P<0.05]和足突融合率(0.80 ±0.07 比0)增高;与糖尿病组比较,二甲双胍组和格列本脲组肾脏基底膜厚度[(151 ±17)与(204 ±22) nm]和足突融合率(0.49 ± 0.04与0.57 ±0.03)降低,且两药物干预组间比较差异均有统计学意义(均P<0.05).结论 二甲双胍具有降糖以外的肾小球足细胞保护作用,可能通过调节肾组织足细胞PCX的表达实现.
目的 觀察二甲雙胍對2型糖尿病大鼠腎小毬足細胞特異性蛋白podocalyxin (PCX)錶達和排洩的影響,瞭解其對腎小毬足細胞的保護作用.方法 高脂餵養結閤腹腔註射小劑量鏈脲佐菌素建立大鼠2型糖尿病模型.25隻造模成功的SD大鼠隨機分為糖尿病組(9隻) ,二甲雙胍組(300 mg· kg-1· d-1,8隻),格列本脲組(5 mg· kg-1 · d-1,8隻);併設正常對照組(8 隻).榦預8週後,檢測大鼠血糖(BG)、糖化血紅蛋白(HbA1c)、尿PCX和尿肌酐的排洩;免疫組化觀察大鼠腎髒PCX蛋白錶達水平;實時定量PCR檢測大鼠PCX mRNA錶達水平;電鏡下觀察大鼠腎髒病理改變.結果 二甲雙胍組、格列本脲組大鼠BG[(9.6 ±1.1)、(9.9 ±1.1)比 (15.6 ±1.6)mmol/L,均P<0.05]和HbA1c[(7.0 ±0.3)%、(8.0 ±1.0)%比(12.4 ±0.6)%,均P<0.05]均顯著低于糖尿病組,但兩藥物榦預組間差異均無統計學意義(均P>0.05).糖尿病組大鼠尿PCX肌酐比高于正常對照組[(697 ±136)比(94 ±25) ng/g,P<0.05],併伴有腎髒組織PCX蛋白(0.75 ±0.11 比3.18 ± 0.14,P<0.05)和mRNA(0.08 ±0.09比1.00 ±0.02,P<0.05)錶達減少.二甲雙胍和格列本脲治療後上述指標均顯著改善(均P<0.05),且二甲雙胍組尿PCX肌酐比[(404 ±83)比(516 ±38) ng/g]、腎髒組織PCX蛋白(1.54 ±0.06比1.06 ±0.10)和mRNA(0.23 ±0.01比0.16 ±0.04)與格列本脲組比較差異均有統計學意義(均P<0.05).進一步觀察髮現,糖尿病組與正常對照組比較腎髒基底膜厚度[(267 ±22) 比(106 ±10) nm,P<0.05]和足突融閤率(0.80 ±0.07 比0)增高;與糖尿病組比較,二甲雙胍組和格列本脲組腎髒基底膜厚度[(151 ±17)與(204 ±22) nm]和足突融閤率(0.49 ± 0.04與0.57 ±0.03)降低,且兩藥物榦預組間比較差異均有統計學意義(均P<0.05).結論 二甲雙胍具有降糖以外的腎小毬足細胞保護作用,可能通過調節腎組織足細胞PCX的錶達實現.
목적 관찰이갑쌍고대2형당뇨병대서신소구족세포특이성단백podocalyxin (PCX)표체화배설적영향,료해기대신소구족세포적보호작용.방법 고지위양결합복강주사소제량련뇨좌균소건립대서2형당뇨병모형.25지조모성공적SD대서수궤분위당뇨병조(9지) ,이갑쌍고조(300 mg· kg-1· d-1,8지),격렬본뇨조(5 mg· kg-1 · d-1,8지);병설정상대조조(8 지).간예8주후,검측대서혈당(BG)、당화혈홍단백(HbA1c)、뇨PCX화뇨기항적배설;면역조화관찰대서신장PCX단백표체수평;실시정량PCR검측대서PCX mRNA표체수평;전경하관찰대서신장병리개변.결과 이갑쌍고조、격렬본뇨조대서BG[(9.6 ±1.1)、(9.9 ±1.1)비 (15.6 ±1.6)mmol/L,균P<0.05]화HbA1c[(7.0 ±0.3)%、(8.0 ±1.0)%비(12.4 ±0.6)%,균P<0.05]균현저저우당뇨병조,단량약물간예조간차이균무통계학의의(균P>0.05).당뇨병조대서뇨PCX기항비고우정상대조조[(697 ±136)비(94 ±25) ng/g,P<0.05],병반유신장조직PCX단백(0.75 ±0.11 비3.18 ± 0.14,P<0.05)화mRNA(0.08 ±0.09비1.00 ±0.02,P<0.05)표체감소.이갑쌍고화격렬본뇨치료후상술지표균현저개선(균P<0.05),차이갑쌍고조뇨PCX기항비[(404 ±83)비(516 ±38) ng/g]、신장조직PCX단백(1.54 ±0.06비1.06 ±0.10)화mRNA(0.23 ±0.01비0.16 ±0.04)여격렬본뇨조비교차이균유통계학의의(균P<0.05).진일보관찰발현,당뇨병조여정상대조조비교신장기저막후도[(267 ±22) 비(106 ±10) nm,P<0.05]화족돌융합솔(0.80 ±0.07 비0)증고;여당뇨병조비교,이갑쌍고조화격렬본뇨조신장기저막후도[(151 ±17)여(204 ±22) nm]화족돌융합솔(0.49 ± 0.04여0.57 ±0.03)강저,차량약물간예조간비교차이균유통계학의의(균P<0.05).결론 이갑쌍고구유강당이외적신소구족세포보호작용,가능통과조절신조직족세포PCX적표체실현.
Objective To observe the effects of metformin (MET) on podocalyxin (PCX) expression in renal tissue from type 2 diabetes mellitus (T2DM) model rats and investigate its protective effects against glomerular podocyte injury.Method The rat model of T2DM was established by feeding with high-fat diet and intraperitoneal injection of low dose of streptozotocin (STZ).All the rats were divided into four groups:diabetic group (n=9), metformin group (300 mg· kg -1· d-1, n=8), glibenclamide group (5 mg· kg -1· d-1, n=8) and normal group (n=8).After 8 weeks, urinary PCX and creatinine, blood glucose(BG) and glycated hemoglobin (HbA1c) were detected in all the rats.Immunohistochemistry was used to observe the protein expression of PCX in renal tissue.Real-time polymerase chain reaction (PCR) was performed to detect mRNA expression of PCX.Pathological changes of renal tissue were observed by electron microscope.Results Metformin and glyburide treatment decreased the levels of BG and HbA 1c [(9.6 ±1.1) and (9.9 ±1.1) vs (15.6 ±1.6) mmol/L, (7.0 ±0.3)% and (8.0 ±1.0)% vs (12.4 ±0.6)%, all P<0.05], compared with diabetes group, while there was no statistically significant difference between the two intervention groups (P >0.05).The level of urinary PCX/urinary creatinine(UPCR) in diabetic rats were higher than that of normal group [ (697 ±136) vs (94 ±25) ng/g, P<0.05), meanwhile the levels of protein and mRNA expression of PCX in kidney tissue reduced remarkably [(0.75 ±0.11) vs (3.18 ±0.14), (0.08 ±0.09) vs (1.00 ±0.02), both P<0.05].Above-mentioned indicators could be ameliorated by metformin and glyburide treatment compared to normal group (P<0.05), and there were statistically significant difference between the two intervention groups [(404 ±83) vs (516 ± 38) ng/g, (1.54 ±0.06) vs(1.06 ±0.10), (0.23 ±0.01) vs (0.16 ±0.04), all P<0.05)].Further observation found that basement membrane thickness of kidney [(267 ±22) vs (106 ±10)nm)]and fusion rate of foot process (0.80 ±0.07 vs 0)increased in the rats of diabetic group, and metformin or glyburide treatment can significantly reduced the above changes (P <0.05) , additionally , the changes were remarkable different between metformin and glyburide group [ (151 ±17) vs (204 ±22) nm, (0.49 ± 0.04) vs (0.57 ±0.03), both P<0.05)].Conclusion Metformin has protective effect on glomerular podocytes by regulating the expression of PCX in renal tissue , independent of its hypoglycemic effect.
