RouxenY胃转流术对代谢综合征大鼠糖脂代谢及过氧化物酶体增长因子活化受体γ表达的影响

Effects of RouxenY gastric bypass surgery on the glycolipid metabolism and expression of peroxisome proliferatoractivatived receptorγ protein in rats with metabolic syndrome

  • 摘要: 目的:探讨RouxenY胃转流术对代谢综合征大鼠肥胖相关指标、糖脂代谢指标、器官脂肪组织过氧化物酶体增长因子活化受体γ(PPARγ)蛋白表达的影响。
    方法:40只健康雄性7~8周龄SD大鼠,适应性喂养1周后,选取30只,予高糖高脂高盐饲料配合20%蔗糖水喂养12周,筛选出24只符合标准的代谢综合征模型大鼠,按完全随机区段分组法分为假手术组(11只)和手术组(13只)。假手术组行胃窦十二指肠离断原位吻合术,手术组行RouxenY胃转流术。其余10只健康SD大鼠予标准饮食喂养设为正常组。术后5周处死大鼠,立即取肠系膜、双肾周及双侧附睾旁脂肪组织,采用Western blot法检测大鼠器官脂肪组织PPARγ蛋白含量。观察指标包括:(1)肥胖相关指标:术前及术后5周进食量、体质量、腹围、Lee′s指数,术后5周器官脂肪质量、器官脂肪系数。(2)糖脂代谢指标:术前及术后5周空腹血糖、血清胰岛素、稳态胰岛素评价指数(HOMAIR)、TC、TG、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、血清游离脂肪酸。(3)术后5周器官脂肪组织PPARγ蛋白含量。正态分布的计量资料以±s表示,多组间比较采用方差分析,两组间比较采用LSDt检验,重复测量数据采用重复测量方差分析。
    结果:手术组大鼠术后1周死亡3只,死亡率为3/13;其余各组无大鼠死亡。正常组大鼠进食量、体质量、腹围、Lee′s指数术前分别为(269±15)g、(499±46)g、(182±04)cm、309±9,术后5周分别为(277±21)g、(547±43)g、(186±05)cm、312±8;假手术组大鼠上述指标术前分别为(261±18)g、(584±42)g、(193±06)cm、(317±13),术后5周分别为(288±17)g、(677±39)g、(206±07)cm、334±11;手术组大鼠上述指标术前分别为(259±21)g、(579±47)g、(194±05)cm、311±5,术后5周分别为(175±08)g、(470± 40)g、(181±04)cm、302±4;上述指标术前3组比较,差异均无统计学意义(F=0821,0784,0813,0642,P>005);上述指标术前至术后5周变化趋势,3组比较,差异均有统计学意义(F=4650,3852,4362,4042,P<005)。正常组大鼠术后5周器官脂肪质量、器官脂肪系数分别为(34± 6)g、62%±05%,假手术组分别为(55±6)g、82%±06%,手术组分别为(28±6)g、61%±05%;3组大鼠上述2个指标比较,差异均有统
    计学意义(F=16750,14686,P<005)。术后5周器官脂肪质量正常组与假手术组比较,差异有统计学意义(t=4287,P<005);正常组与手术组比较,差异无统计学意义(t=1225,P>005);假手术组与手术组比较,差异有统计学意义(t=5511,P<005)。术后5周器官脂肪系数正常组与假手术组比较,差异有统计学意义(t=4435,P<005);正常组与手术组比较,差异无统计学意义(t=0245, P>005);假手术组与手术组比较,差异有统计学意义(t=4657,P<005)。正常组大鼠空腹血糖、血清胰岛素、HOMAIR、TC、TG、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、血清游离脂肪酸术前分别为(43±09)mmol/L、(151±49)μmol/L、219±143、(112±013)mmol/L、(13±05)mmol/L、(132±019)mmol/L、(09±04)mmol/L、(131±17)mmol/L,术后5周分别为(43±12)mmol/L、(148± 53)μmol/L、229±137、(107±016)mmol/L、(12±07)mmol/L、(128±022)mmol/L、(08± 05)mmol/L、(134±19)mmol/L;假手术组大鼠上述指标术前分别为(61±07)mmol/L、(301± 18)μmol/L、786±156、(332±014)mmol/L、(25±06)mmol/L、(081±021)mmol/L、(28± 07)mmol/L、(178±18)mmol/L,术后5周分别为(61±07)mmol/L、(316±21)μmol/L、850±166、 (343±012)mmol/L、(27±05)mmol/L、(084±024)mmol/L、(31±05)mmol/L、(182±19)mmol/L;手术组大鼠上述指标术前分别为(62±06)mmol/L、(296±27)μmol/L、743±103、(336± 015)mmol/L、(26±05)mmol/L、(079±017)mmol/L、(29±06)mmol/L、(180±17)mmol/L,术后5周分别为(45±08)mmol/L、(195±10)μmol/L、517±025、(146±008)mmol/L、(15±04)mmol/L、(109±018)mmol/L、(12±03)mmol/L、(146±16)mmol/L;上述指标术前3组比较,差异均无统计学意义(F=0625,0746,0813,0649,0754,0823,0587,0648,P>005);术前至术后5周变化趋势,3组比较,差异均有统计学意义(F=4714,14921,18971,20544,5731,6143,10276,6607,P<005)。正常组、假手术组、手术组大鼠术后5周器官脂肪组织PPARγ蛋白含量分别为079±026、022±017、118±037,3组比较,差异有统计学意义(F=8988,P<005);正常组与假手术组比较,差异有统计学意义(t=3178,P<005);正常组与手术组比较,差异无统计学意义(t=1494,P>005);假手术组与手术组比较,差异有统计学意义(t=4084,P<005)。
    结论:RouxenY胃转流术可减少代谢综合征大鼠器官脂肪堆积,改善糖脂代谢和胰岛素抵抗,上调器官脂肪组织PPARγ表达。

     

    Abstract: Objective:To investigate the effects of RouxenY gastric bypass surgery on the obesityrelated indexes, glycolipid metabolism indexes and expression of peroxisome proliferatoractivatived receptorγ (PPARγ) protein in visceral adipose tissues of rats with metabolic syndrome.
    Methods:After 40 Sprague Dawley (SD) male rats with the age of 7-8 weeks were adaptively fed for 1 week, 30 rats were selected randomly and were fed with highfat, high glucose and high salt diet combined with sucrose water for 12 weeks, and then 24 rats with metabolic syndrome were screened for eligibility and were allocated into the model group (n=11) and the operation group (n=13) 〖HQK〗based on the randomized complete block design. Rats of the model group and operation group received transection and reanastomosis of the gastrointestinal tract and RouxenY gastric bypass surgery, respectively. Other 10 rats receiving normal feeding were divided into the control group. After executing rats at postoperative week 5, the levels of PPARγ protein in visceral adipose tissues around mesentery, double kidneys and bilateral epididymis were detected by the Western blot. Observation indexes: (1) obesityrelated indexes included food intake before operation and at postoperative week 5, body weight, abdominal circumference, Lee′s index, visceral adipose weight at postoperative week 5 and visceral adipose coefficient. (2) Glycolipid metabolism indexes included fasting plasma glucose before operation and at postoperative week 5, fasting serum insulin, homeostasis model assessmentinsulin resistance (HOMAIR), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC) and free fatty acid (FFA). (3) Level of PPARγ protein in visceral adipose tissues at postoperative week 5.  Measurement data with normal distribution were presented as ±s. Comparison among groups was analyzed using the ANOVA, and comparison between groups was analyzed using the LSDt test. Repeated measures data were analyzed by the repeated measures ANOVA.
    Results:Three rats in the operation group were dead at postoperative week 1 with a mortality of 3/13 and no death was occurred in other groups. The consumption of food, body weight, abdominal circumference, Lee′s index before operation and at postoperative week 5 were (26.9±1.5)g, (499±46)g, (18.2±0.4)cm, 309±9 and (27.7±2.1)g, (547±43)g, (18.6±0.5)cm, 312±8 in the control group, (26.1±1.8)g, (584±42)g, (19.3±0.6)cm, 317±13 and (28.8±1.7)g, (677±39)g, (20.6±0.7)cm, 334±11 in the model group, (25.9±2.1)g, (579±47)g, (19.4±0.5)cm, 311±5 and (17.5±0.8)g, (470±40)g, (18.1±0.4)cm, 302±4 in the operation group, respectively, with no significant difference in the above indexes before operation among the 3 groups (F=0.821, 0.784, 0.813, 0.642, P>0.05), and with significant differences in the changing trends of above indexes of 3 groups between before operation and postoperative week 5 (F=4.650, 3.852, 4.362, 4.042, P<0.05). The visceral adipose weight at postoperative week 5 and visceral adipose coefficient were (34±6)g and 6.2%±0.5% in the control group, (55±6)g and 8.2%±0.6% in the model group and (28±6)g and 6.1%±0.5% in the operation group, respectively, with significant differences in the above indexes (F=16.750, 14.686, P<0.05). There were significant differences in the visceral adipose weight at postoperative week 5 not only between control group and model group but also between model group and operation group (t=4.287, 5.511, P<0.05), and no significant difference between control group and operation group (t=1.225, P>0.05). There were significant differences in the visceral adipose coefficient at postoperative week 5 not only between control group and model group but also between model group and operation group (t=4.435, 4.657, P<0.05), and no significant difference between control group and operation group (t=0.245, P>0.05). The fasting plasma glucose, fasting serum insulin, HOMAIR, TC, TG, HDLC, LDLC and FFA before operation and at postoperative week 5 were (4.3± 0.9)mmol/L, (15.1±4.9)μmol/L, 2.19±1.43, (1.12±0.13)mmol/L, (1.3±0.5)mmol/L, (1.32± 0.19)mmol/L, (0.9±0.4)mmol/L, (131±17)mmol/L and (4.3±1.2)mmol/L, (14.8±5.3)μmol/L, 2.29±1.37, (1.07±0.16)mmol/L, (1.2±0.7)mmol/L, (1.28±0.22)mmol/L, (0.8±0.5)mmol/L and (134±19)mmol/L in the control group, (6.1±0.7)mmol/L, (30.1±1.8)μmol/L, 7.86±1.56, (3.32± 0.14)mmol/L, (2.5±0.6)mmol/L, (0.81±0.21)mmol/L, (2.8±0.7)mmol/L, (178±18)mmol/L and (6.1±0.7)mmol/L, (31.6±2.1)μmol/L, 8.50±1.66, (3.43±0.12)mmol/L, (2.7±0.5)mmol/L, (0.84±0.24)mmol/L, (3.1±0.5)mmol/L, (182±19)mmol/L in the model group, (6.2±0.6)mmol/L, (29.6±2.7)μmol/L, 7.43±1.03, (3.36±0.15)mmol/L, (2.6±0.5)mmol/L, (0.79±0.17)mmol/L, (2.9±0.6)mmol/L, (180±17)mmol/L and (4.5±0.8)mmol/L, (19.5±1.0)μmol/L, 5.17±0.25, (1.46±0.08)mmol/L, (1.5±0.4)mmol/L, (1.09±0.18)mmol/L, (1.2±0.3)mmol/L, (146±16)mmol/L in the operation group, respectively . There was no significant difference in the above indexes before operation among the 3 groups (F=0.625, 0.746, 0.813, 0.649, 0.754, 0.823, 0.587, 0.648, P>0.05). There were significant differences in the changing trends from before operation to postoperative week 5 among the 3 groups (F=4.714, 14.921, 18.971, 20.544, 5.731, 6.143, 10.276, 6.607, P<0.05). Level of PPARγ protein in visceral adipose tissues at postoperative week 5 in the control group, model group and operation group were 0.79±0.26, 0.22±0.17, 1.18±0.37, respectively, showing a significant difference among the 3 groups (F=8.988, P<0.05). There were significant differences in the level of PPARγ protein not only between control group and model group but also between model group and operation group (t=3.178, 4.084, P<0.05), and no significant difference between control group and operation group (t=1.494, P>0.05).
     Conclusion:RouxenY gastric bypass surgery can reduce the visceral fat accumulation of rats with metabolic syndrome, improve metabolism of glucose and lipid and increase expression of PPARγ protein in visceral adipose tissue.

     

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