糖尿病,2型%糖尿病肾病%Roux-en-Y胃旁路术
糖尿病,2型%糖尿病腎病%Roux-en-Y胃徬路術
당뇨병,2형%당뇨병신병%Roux-en-Y위방로술
Diabetes mellitus,type 2%Diabetic nephropathy%Roux-en-Y gastric bypass
目的 探讨Roux-en-Y胃旁路术对2型糖尿病大鼠肾功能的影响.方法 采用高脂高糖饮食联合腹腔注射小剂量链脲佐菌素(streptozocin,STZ,35μg/g)方法建立2型糖尿病大鼠模型.将造模成功的糖尿病SD大鼠分为3组:糖尿病组(8只),假手术组(8只),手术组(14只);另取正常SD大鼠作为正常组(8只).术前、术后8周检测大鼠空腹血糖,术前及术后4、8周测定血清BUN、Cr;术后8周取肾组织进行病理组织学观察,计算肾脏质量指数;免疫组织化学染色方法检测肾组织纤连蛋白、Ⅳ型胶原和TGF-β1的表达,采用Real-time PCR和Western blot检测MMP-2、MMP-9 mRNA和蛋白的表达.多组比较采用单因素方差分析,两两比较采用LSD检验.结果术后8周,糖尿病组大鼠血糖、BUN、Cr、肾脏质量指数分别为(15.9±1.6) mmol/L、(9.2±0.6) mmol/L、(44 ±4) μmol/L、(10.7±1.5)mg/g,手术组大鼠分别为(5.9±0.7)mmol/L、(6.6±0.4) mmol/L、(30 ±2) μmol/L、(8.6±0.6) mg/g,两组比较,差异有统计学意义(P＜0.05).与正常组比较,糖尿病组、假手术组大鼠肾小球体积增大,系膜增生;手术组有明显改善.正常组大鼠肾脏皮质纤连蛋白、Ⅳ型胶原、TGF-β1免疫组织化学染色积分光密度值、MMP-2、MMP-9 mRNA和蛋白的表达水平分别为664±23、86±5、52 ±6、1.00 ±0.04、64±4、1.00±0.20、48 ±5,糖尿病组大鼠分别为1665±44、789±66、459±35、0.52±0.13、51 ±6、0.36 ±0.05、38 ±4,假手术组大鼠分别为1701±55、754±49、425±42、0.54±0.19、48 ±5、0.43±0.09、39±4,手术组大鼠分别为1105±61、195±11、147±16、1.53±0.29、63 ±5、1.11±0.14、49±5,4组比较,差异均有统计学意义(F=1340.30,4982.50,2025.10,654.19,13.58,610.74,7.86,P＜0.05).两两比较,差异均有统计学意义(P＜0.05).结论Roux-en-Y胃旁路术可改善糖尿病大鼠肾功能,减少细胞外基质沉积,其作用机制可能与抑制TGF-β1表达和上调MMP-2、MMP-9 mRNA和蛋白水平有关.
目的 探討Roux-en-Y胃徬路術對2型糖尿病大鼠腎功能的影響.方法 採用高脂高糖飲食聯閤腹腔註射小劑量鏈脲佐菌素(streptozocin,STZ,35μg/g)方法建立2型糖尿病大鼠模型.將造模成功的糖尿病SD大鼠分為3組:糖尿病組(8隻),假手術組(8隻),手術組(14隻);另取正常SD大鼠作為正常組(8隻).術前、術後8週檢測大鼠空腹血糖,術前及術後4、8週測定血清BUN、Cr;術後8週取腎組織進行病理組織學觀察,計算腎髒質量指數;免疫組織化學染色方法檢測腎組織纖連蛋白、Ⅳ型膠原和TGF-β1的錶達,採用Real-time PCR和Western blot檢測MMP-2、MMP-9 mRNA和蛋白的錶達.多組比較採用單因素方差分析,兩兩比較採用LSD檢驗.結果術後8週,糖尿病組大鼠血糖、BUN、Cr、腎髒質量指數分彆為(15.9±1.6) mmol/L、(9.2±0.6) mmol/L、(44 ±4) μmol/L、(10.7±1.5)mg/g,手術組大鼠分彆為(5.9±0.7)mmol/L、(6.6±0.4) mmol/L、(30 ±2) μmol/L、(8.6±0.6) mg/g,兩組比較,差異有統計學意義(P＜0.05).與正常組比較,糖尿病組、假手術組大鼠腎小毬體積增大,繫膜增生;手術組有明顯改善.正常組大鼠腎髒皮質纖連蛋白、Ⅳ型膠原、TGF-β1免疫組織化學染色積分光密度值、MMP-2、MMP-9 mRNA和蛋白的錶達水平分彆為664±23、86±5、52 ±6、1.00 ±0.04、64±4、1.00±0.20、48 ±5,糖尿病組大鼠分彆為1665±44、789±66、459±35、0.52±0.13、51 ±6、0.36 ±0.05、38 ±4,假手術組大鼠分彆為1701±55、754±49、425±42、0.54±0.19、48 ±5、0.43±0.09、39±4,手術組大鼠分彆為1105±61、195±11、147±16、1.53±0.29、63 ±5、1.11±0.14、49±5,4組比較,差異均有統計學意義(F=1340.30,4982.50,2025.10,654.19,13.58,610.74,7.86,P＜0.05).兩兩比較,差異均有統計學意義(P＜0.05).結論Roux-en-Y胃徬路術可改善糖尿病大鼠腎功能,減少細胞外基質沉積,其作用機製可能與抑製TGF-β1錶達和上調MMP-2、MMP-9 mRNA和蛋白水平有關.
목적 탐토Roux-en-Y위방로술대2형당뇨병대서신공능적영향.방법 채용고지고당음식연합복강주사소제량련뇨좌균소(streptozocin,STZ,35μg/g)방법건립2형당뇨병대서모형.장조모성공적당뇨병SD대서분위3조:당뇨병조(8지),가수술조(8지),수술조(14지);령취정상SD대서작위정상조(8지).술전、술후8주검측대서공복혈당,술전급술후4、8주측정혈청BUN、Cr;술후8주취신조직진행병리조직학관찰,계산신장질량지수;면역조직화학염색방법검측신조직섬련단백、Ⅳ형효원화TGF-β1적표체,채용Real-time PCR화Western blot검측MMP-2、MMP-9 mRNA화단백적표체.다조비교채용단인소방차분석,량량비교채용LSD검험.결과술후8주,당뇨병조대서혈당、BUN、Cr、신장질량지수분별위(15.9±1.6) mmol/L、(9.2±0.6) mmol/L、(44 ±4) μmol/L、(10.7±1.5)mg/g,수술조대서분별위(5.9±0.7)mmol/L、(6.6±0.4) mmol/L、(30 ±2) μmol/L、(8.6±0.6) mg/g,량조비교,차이유통계학의의(P＜0.05).여정상조비교,당뇨병조、가수술조대서신소구체적증대,계막증생;수술조유명현개선.정상조대서신장피질섬련단백、Ⅳ형효원、TGF-β1면역조직화학염색적분광밀도치、MMP-2、MMP-9 mRNA화단백적표체수평분별위664±23、86±5、52 ±6、1.00 ±0.04、64±4、1.00±0.20、48 ±5,당뇨병조대서분별위1665±44、789±66、459±35、0.52±0.13、51 ±6、0.36 ±0.05、38 ±4,가수술조대서분별위1701±55、754±49、425±42、0.54±0.19、48 ±5、0.43±0.09、39±4,수술조대서분별위1105±61、195±11、147±16、1.53±0.29、63 ±5、1.11±0.14、49±5,4조비교,차이균유통계학의의(F=1340.30,4982.50,2025.10,654.19,13.58,610.74,7.86,P＜0.05).량량비교,차이균유통계학의의(P＜0.05).결론Roux-en-Y위방로술가개선당뇨병대서신공능,감소세포외기질침적,기작용궤제가능여억제TGF-β1표체화상조MMP-2、MMP-9 mRNA화단백수평유관.
Objective To investigate the effects of Roux-en-Y gastric bypass on the renal function of rats with type 2 diabetes mellitus.Methods Rat models of type 2 diabetes mellitus were established by intraperitoneal injection of streptozotocin (35 μg/g) and a high-fat diet.All the rats were randomly divided into diabetes group (8 rats),sham operation group (8 rats) and Roux-en-Y gastric bypass group (14 rats).Another 8 normal rats were selected in the normal control group.The level of fasting blood glucose was detected preoperatively and 8 weeks after the operation.The levels of blood urea nitrogen and creatinine were detected preoperatively and 4 and 8 weeks after the operation.Pathological changes of the renal tissue were observed and the indexes of kidney hypertrophy were analyzed 8 weeks after the operation.The expressions of fibronectin,type Ⅳ collagen and TGF-β1 were detected by immunohistochemical staining.The mRNA and protein expressions of MMP-2 and MMP-9 were detected by Real-time PCR and Western blot,respectively.All data were analyzed using the analysis of variance or LSD test.Results In postoperative week 8,the levels of fasting glucose,blood urea nitrogen,creatinine and index of kidney hypertrophy were (15.9 ± 1.6) mmol/L,(9.2 ± 0.6) mmol/L,(44 ± 4) μmol/L and (10.7 ± 1.5)mg/g in the diabetes group,and (5.9 ±0.7) mmol/L,(6.6 ±0.4) mmol/L,(30 ±2) μmol/L and (8.6 ± 0.6)mg/g in the Roux-en-Y gastric bypass group,with significant difference between the 2 groups (P ＜ 0.05).Compared with the normal control group,the volumes of glomerulus of kidney in the diabetes group and the sham operation group were greater,and mesangial proliferation was detected.The integral optical density of fibronectin,type Ⅳ collagen,TGF-β1,the mRNA and protein expressions of MMP-2 and MMP-9 were 664 ± 23,86 ± 5,52 ± 6,1.00 ± 0.04,64 ± 4,1.00 ± 0.20,48 ± 5 in the normal control group,and 1665 ± 44,789 ±66,459 ±35,0.52 ±0.13,51 ±6,0.36 ±0.05,38 ±4 in the diabetes group,and 1701 ±55,754 ±49,425 ± 42,0.54 ± 0.19,48 ± 5,0.43 ± 0.09,39 ± 4 in the sham operation group,and 1105 ± 61,195 ± 11,147 ± 16,1.53 ±0.29,63 ±5,1.11 ±0.14,49 ±5 in the Roux-en-Y gastric bypass group,with significant difference between the 4 groups (F =1340.30,4982.50,2025.10,654.19,13.58,610.74,7.86,P ＜0.05).Significant difference was detected in pairwise comparison (P ＜ 0.05).Conclusion Roux-en-Y gastric bypass surgery can improve the renal function of rats with type 2 diabetes mellitus,reduce deposition of extracellular matrix.Its mechanism may be related to inhibition of TGF-β1 expression and increase of MMP-2 and MMP-9 mRNA and protein expressions.
