胃旁路手术对高尿酸血症大鼠代谢的影响
发布时间：2018-07-26 17:18
【摘要】：目的:探讨胃旁路手术对高尿酸血症大鼠血尿酸、血脂、血糖等代谢指标的影响,分析可能机制。方法:8周龄的雄性Wistar大鼠40只随机分组为空白对照组(C,n=10)和模型组(M,n=30)。模型组给予高嘌呤饮食加腺嘌呤混悬液灌胃处理建立高尿酸血症模型,空白对照组正常饮食。建模成功后将模型组随机分为高尿酸血症组(H,n=10)、假手术组(Sham,n=10)和胃旁路手术组(RYGB,n=10),并对其进行相应处理,手术后大鼠普通饮食。分别于手术前,术后2周、4周、6周和8周大鼠静脉取血,检测其血尿酸、血糖、甘油三酯、胆固醇、肌酐、尿素氮和胰岛素水平的变化,并计算胰岛素抵抗指数HOMA-IR值比较胰岛素抵抗的差异。手术前留取粪便标本,术后8周后处死大鼠,留取粪便、相应组织器官和血液标本,留待菌群、代谢组学和相关组织病理的检测,进一步探究可能的机制。结果:手术前,四组大鼠的体重无显著统计学差异(分别为327.6±16.37 vs 313.8±17.32 vs 316.5±16.96 vs 319.5±19.98,p均0.05)。手术8周后,RYGB组体重显著下降,明显低于其他三组(分别为248.6±15.08 vs 416.2±21.08,248.6±15.08 vs411.7±22.82和248.6±15.08 vs 398.3±18.81,p均0.05)。建模4周后,模型组大鼠与空白对照组相比,血尿酸水平明显升高(235.33±17.85 vs 108.37±13.64,p0.05),表示成功建立高尿酸血症大鼠模型。手术后8周,3组模型组大鼠的血尿酸水平均有不同程度的下降,然而RYGB组血尿酸水平下降更明显,接近于对照组的正常水平(114.03±9.21 vs 122.21±10.33,p0.05),而高尿酸组和假手术组仍高于空白对照组(分别为184.67±11.53 vs 114.03±9.21;和189.32±15.81 vs 114.03±9.21,p均005),而伴随血尿酸的下降,肌酐和尿素氮也出现降低,其中胃旁路组与空白对照组无明显差异(分别为20.82±4.67 vs 19.20±3.12和8.02±1.66 vs 7.17±1.64,p均大于0.05)。而对于其他的代谢指标,血糖在手术前3个实验组与空白对照组有明显的差异(分别为6.61±0.39,6.51±0.47,6.59±0.57 vs 4.26±0.58,p均0.05),而在术后8周,胃旁路手术组明显下降,与空白对照组无差异(4.67±0.43 vs 4.01±0.54,p0.05),其余高尿酸组和假手术组无明显变化,与空白对照组有明显差异(分别为6.69±0.48,6.86±0.52 vs 4.01±0.54,p均0.05);血甘油三酯在术前,3个实验组与空白对照组有明显差异(分别为1.14±0.24,1.20±0.22,1.18±0.18 vs 0.58±0.24,p均0.05),手术后,3个实验组较术前均有不用程度的下降,3个组与空白对照组无差异(分别为0.86±0.22,0.89±0.18,0.66±0.21 vs 0.61±0.19,p均0.05),而胃旁路组较其余两个实验组下降趋势更为明显,下降幅度更大;血胆固醇水平3组手术后均有下降,其中胃旁路组下降显著,与空白对照组无显著差异(1.51±0.28 vs1.43±0.27,p0.05),其余两组与空白对照组相比仍有差异(分别为2.16±0.29,2.19±0.30 vs 1.43±0.27,p均0.05)。通过计算胰岛素抵抗指数HOMA-IR值我们发现,术前3个实验组与空白对照组出现显著性差异(分别为3.92±0.52,3.86±0.49,3.82±0.51 vs 2.24±0.38,p均0.05),术后8周,胃旁路组胰岛素抵抗明显缓解,与空白对照组无明显差异(2.19±0.42 vs 2.08±0.41,p0.05),而高尿酸组和假手术组仍然高于空白对照组(分别为3.45±0.57,3.51±0.52 vs 2.08±0.41,p均0.05).结论:胃旁路手术能够明显改善高尿酸血症大鼠的血尿酸水平,同时纠正高尿酸血症血糖、血脂的代谢紊乱和肾功能的影响,缓解胰岛素抵抗。其机制可能与胃旁路手术后肠道激素的分泌改变和菌群及产物的变化引起代谢和炎症通路的缓解有关。
[Abstract]:Objective: To investigate the effect of gastric bypass surgery on the metabolic indexes of uric acid, blood lipid and blood glucose in hyperuricemia rats, and to analyze the possible mechanism. Methods: 40 male Wistar rats of 8 weeks old were randomly divided into blank control group (C, n=10) and model group (M, n=30). The model group was given high urine with hyperpurine diet plus adenine suspension to establish high uric acid blood. After the modeling success, the model group was randomly divided into the hyperuricemia group (H, n=10), the sham operation group (Sham, n=10) and the gastric bypass surgery group (RYGB, n=10), and the rats were treated accordingly. After the operation, the rats were treated with the normal diet. The blood uric acid was measured at 2 weeks, 4 weeks, 6 weeks and 8 weeks after the operation. The changes in blood sugar, triglyceride, cholesterol, creatinine, urea nitrogen and insulin levels and the difference between the HOMA-IR value of the insulin resistance index and the difference between the insulin resistance were calculated. The rats were left out before the operation and 8 weeks after the operation, the rats were killed, the excrement was left, the corresponding tissues and blood samples were left, the bacteria group, the metabolomics and the related histopathological examination were kept. Test, further explore the possible mechanism. Results: before operation, there was no significant difference in weight between the four groups (327.6 + 16.37 vs, 313.8 + 17.32 vs, 316.5 + 16.96 vs 319.5 + 19.98, and 0.05). After 8 weeks of operation, the body weight of RYGB group was significantly lower than that of other three groups (248.6 + 16.37 + vs + 21.08248.6 + vs411, respectively. .7 + 22.82 and 248.6 + 15.08 vs 398.3 + 18.81, P 0.05). After modeling for 4 weeks, the blood uric acid level in the model group was significantly higher than that in the blank control group (235.33 + 17.85 vs 108.37 +, P0.05), indicating that the hyperuricemia rat model was successfully established. The decrease of serum uric acid level in RYGB group was more obvious, which was close to the normal level of the control group (114.03 + 9.21 vs 122.21 + 10.33, P0.05), while the high uric acid group and sham group were still higher than the blank control group (184.67 + 11.53 vs 114.03 + 9.21 respectively, and 189.32 + 15.81 vs 114.03 + 9.21, P 005), with the decrease of serum uric acid, creatinine and urea nitrogen There was no significant difference between the gastric bypass group and the blank control group (20.82 + 4.67 vs 19.20 + 3.12, 8.02 + 1.66 vs 7.17 + 1.64, P greater than 0.05). For other metabolic indicators, there was a significant difference between the blood sugar and the blank control group before the operation (6.61 + 0.39,6.51 + 0.47,6.59 + 0.57 vs 4.26 +% respectively, respectively). P was 0.05), but in the 8 week after the operation, the gastric bypass surgery group decreased significantly, and no difference was found in the control group (4.67 + 0.43 vs 4.01 + 0.54, P0.05). The other high uric acid group and sham group had no obvious changes, and there was a significant difference between the control group and the blank control group (6.69 + 0.48,6.86 + 0.52 vs 4.01 + 0.54, P mean 0.05). There were significant differences in the blank control group (1.14 + 0.24,1.20 + 0.22,1.18 + 0.18 vs 0.58 + 0.24, P 0.05). After the operation, the 3 experimental groups were less than before the operation, and there was no difference between the 3 groups and the blank control group (0.86 + 0.22,0.89 + 0.18,0.66 + 0.21 vs 0.61 + 0.19, P 0.05), while the gastric bypass group was more than the rest of the experimental group. The decline trend was more obvious and the decrease was greater; the blood cholesterol level 3 groups decreased after operation, and the gastric bypass group decreased significantly, and there was no significant difference from the blank control group (1.51 + 0.28 vs1.43 + 0.27, P0.05). The other two groups were still different from the blank control group (2.16 + 0.29,2.19 + 0.30 vs 1.43 + 0.27, P 0.05). The HOMA-IR value of insulin resistance index was found to show significant difference between the 3 experimental groups and the blank control group (3.92 + 0.52,3.86 + 0.49,3.82 + 0.51 vs 2.24 + 0.38, P 0.05). The insulin resistance in the gastric bypass group was significantly relieved at the end of the operation, and there was no significant difference between the control group and the blank control group (2.19 + 0.42 vs 2.08 +, P0.05), and high urine. The acid group and the sham operation group were still higher than the blank control group (3.45 + 0.57,3.51 + 0.52 vs 2.08 + 0.41, P 0.05 respectively). Conclusion: gastric bypass surgery can obviously improve the level of uric acid in hyperuricemia rats, and correct the hyperuricemia, the metabolic disorder of blood lipid and the effect of renal function, and alleviate the insulin resistance. It is associated with changes in gut hormone secretion and changes in flora and products after gastric bypass surgery, resulting in the release of metabolic and inflammatory pathways.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R589.7;R656.6
本文编号：2146722
[Abstract]:Objective: To investigate the effect of gastric bypass surgery on the metabolic indexes of uric acid, blood lipid and blood glucose in hyperuricemia rats, and to analyze the possible mechanism. Methods: 40 male Wistar rats of 8 weeks old were randomly divided into blank control group (C, n=10) and model group (M, n=30). The model group was given high urine with hyperpurine diet plus adenine suspension to establish high uric acid blood. After the modeling success, the model group was randomly divided into the hyperuricemia group (H, n=10), the sham operation group (Sham, n=10) and the gastric bypass surgery group (RYGB, n=10), and the rats were treated accordingly. After the operation, the rats were treated with the normal diet. The blood uric acid was measured at 2 weeks, 4 weeks, 6 weeks and 8 weeks after the operation. The changes in blood sugar, triglyceride, cholesterol, creatinine, urea nitrogen and insulin levels and the difference between the HOMA-IR value of the insulin resistance index and the difference between the insulin resistance were calculated. The rats were left out before the operation and 8 weeks after the operation, the rats were killed, the excrement was left, the corresponding tissues and blood samples were left, the bacteria group, the metabolomics and the related histopathological examination were kept. Test, further explore the possible mechanism. Results: before operation, there was no significant difference in weight between the four groups (327.6 + 16.37 vs, 313.8 + 17.32 vs, 316.5 + 16.96 vs 319.5 + 19.98, and 0.05). After 8 weeks of operation, the body weight of RYGB group was significantly lower than that of other three groups (248.6 + 16.37 + vs + 21.08248.6 + vs411, respectively. .7 + 22.82 and 248.6 + 15.08 vs 398.3 + 18.81, P 0.05). After modeling for 4 weeks, the blood uric acid level in the model group was significantly higher than that in the blank control group (235.33 + 17.85 vs 108.37 +, P0.05), indicating that the hyperuricemia rat model was successfully established. The decrease of serum uric acid level in RYGB group was more obvious, which was close to the normal level of the control group (114.03 + 9.21 vs 122.21 + 10.33, P0.05), while the high uric acid group and sham group were still higher than the blank control group (184.67 + 11.53 vs 114.03 + 9.21 respectively, and 189.32 + 15.81 vs 114.03 + 9.21, P 005), with the decrease of serum uric acid, creatinine and urea nitrogen There was no significant difference between the gastric bypass group and the blank control group (20.82 + 4.67 vs 19.20 + 3.12, 8.02 + 1.66 vs 7.17 + 1.64, P greater than 0.05). For other metabolic indicators, there was a significant difference between the blood sugar and the blank control group before the operation (6.61 + 0.39,6.51 + 0.47,6.59 + 0.57 vs 4.26 +% respectively, respectively). P was 0.05), but in the 8 week after the operation, the gastric bypass surgery group decreased significantly, and no difference was found in the control group (4.67 + 0.43 vs 4.01 + 0.54, P0.05). The other high uric acid group and sham group had no obvious changes, and there was a significant difference between the control group and the blank control group (6.69 + 0.48,6.86 + 0.52 vs 4.01 + 0.54, P mean 0.05). There were significant differences in the blank control group (1.14 + 0.24,1.20 + 0.22,1.18 + 0.18 vs 0.58 + 0.24, P 0.05). After the operation, the 3 experimental groups were less than before the operation, and there was no difference between the 3 groups and the blank control group (0.86 + 0.22,0.89 + 0.18,0.66 + 0.21 vs 0.61 + 0.19, P 0.05), while the gastric bypass group was more than the rest of the experimental group. The decline trend was more obvious and the decrease was greater; the blood cholesterol level 3 groups decreased after operation, and the gastric bypass group decreased significantly, and there was no significant difference from the blank control group (1.51 + 0.28 vs1.43 + 0.27, P0.05). The other two groups were still different from the blank control group (2.16 + 0.29,2.19 + 0.30 vs 1.43 + 0.27, P 0.05). The HOMA-IR value of insulin resistance index was found to show significant difference between the 3 experimental groups and the blank control group (3.92 + 0.52,3.86 + 0.49,3.82 + 0.51 vs 2.24 + 0.38, P 0.05). The insulin resistance in the gastric bypass group was significantly relieved at the end of the operation, and there was no significant difference between the control group and the blank control group (2.19 + 0.42 vs 2.08 +, P0.05), and high urine. The acid group and the sham operation group were still higher than the blank control group (3.45 + 0.57,3.51 + 0.52 vs 2.08 + 0.41, P 0.05 respectively). Conclusion: gastric bypass surgery can obviously improve the level of uric acid in hyperuricemia rats, and correct the hyperuricemia, the metabolic disorder of blood lipid and the effect of renal function, and alleviate the insulin resistance. It is associated with changes in gut hormone secretion and changes in flora and products after gastric bypass surgery, resulting in the release of metabolic and inflammatory pathways.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R589.7;R656.6
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