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预防医学  2019, Vol. 31 Issue (1): 15-19    DOI: 10.19485/j.cnki.issn2096-5087.2019.01.004
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血糖波动对糖尿病大鼠肝脏TLR4和TNF-α表达的影响
胡瑜洁1, 姚晓霖2, 钟涛3
1.杭州市妇产科医院检验科,浙江 杭州 310008;
2.浙江大学医学院附属第一医院;
3.浙北明州医院
Effects of blood glucose fluctuation on the expression of TLR4 and TNF-α in the liver of diabetic rats
HU Yu-jie*, YAO Xiao-lin, ZHONG Tao
*Department of Clinical Laboratory,Hangzhou Obstetrics and Gynecology Hospital,Hangzhou,Zhejiang 310008,China
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摘要 目的 探讨血糖波动对糖尿病大鼠肝脏TLR4和TNF-α表达的影响。方法 用雄性SD大鼠建立糖尿病大鼠模型,随机分为持续性高血糖(MS)组和波动性高血糖(MF)组,各20只,继续予高脂高糖饮食,MF组交替腹腔注射葡萄糖及皮下注射短效胰岛素;另选10只大鼠设为空白对照组。造模6周后,测定大鼠一般体征、血糖、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、谷丙转氨酶(ALT)和谷草转氨酶(AST);采用RT-PCR法检测肝组织TLR4、TNF-α的mRNA表达情况;HE染色观察肝脏病理改变。结果 与对照组相比,MS组大鼠一直处于高血糖状态,而MF组大鼠血糖在峰值和低谷之间波动;MS、MF组大鼠体质量增加缓慢,TC、TG、LDL-C显著升高,HDL-C显著降低(均P<0.05);MS、MF组大鼠ALT、AST活性显著增加,且MF组较MS组增加更明显(均P<0.05);MS、MF组大鼠肝组织TLR4和TNF-α的mRNA表达量增加,MF组较MS组增加更明显(均P<0.05);MF组大鼠肝细胞脂滴沉积程度更大,肝细胞索排列紊乱,脂滴空泡化严重,MS组和MF组病变率分别为83.30%和100.00%。结论 糖尿病血糖波动大鼠模型伴有脂代谢异常与肝损伤,TLR4和TNF-α在血糖波动大鼠中表达增加,可能参与血糖波动加重糖尿病肝损伤的过程。
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胡瑜洁
姚晓霖
钟涛
关键词 血糖2型糖尿病肝损伤TLR4TNF-α    
AbstractObjective To investigate the effect of blood glucose fluctuation on the expression of toll-like receptor 4(TLR4)and tumour necrosis factor-α(TNF-α)in the liver of diabetic rats .Methods The adult male Sprague-Dawley(SD)rats were used to establish diabetic rats model and then they were randomly assigned to sustained hyperglycemia group(MS group,n=20) and fluctuating hyperglycemia group(MF group,n=20). The two groups continued high-fat and high-sugar diet,while MF group alternately received intraperitoneal injection of glucose and subcutaneous injection of short-acting insulin. Another 10 SD rats were assigned to the control group. After 6 weeks,the physical signs,blood glucose,triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)of the rats were measured;the mRNA expression of TLR4 and TNF-α in liver tissues were detected by reverse transcription-polymerase chain reaction (RT-PCR);pathological changes of liver tissues were observed after HE staining .Results Compared with the control group,the rats in the MS group were always at the hyperglycemia status,the blood glucose of the rats in the MF group drifted between the peak and the trough. The weight growth of the rats in the MS group and MF group were slower. The levels of TC,TG and LDL-C significantly increased and the level of HDL-C significantly decreased in the MS group and MF group (all P<0.05). The activities of ALT and AST increased both in the MS group and MF group,with the MF group increased more significantly(P<0.05). The mRNA expression levels of TLR4 and TNF-α in liver tissues of the rats in MS group and MF group increased,with the MF group increased more significantly(P<0.05). HE staining results showed that the liver cells of the rats in the MF group had more lipid droplet deposition,with the disordered hepatocyte line arrangement and more severe lipid droplet vacuolation. The lesion rate of the MS group and MF group were 83.30% and 100.00% .Conclusion The rats in this model showed signs of hyperglycemia complicated by dyslipidemia and liver injury. The expression of TLR4 and TNF-α increased in rats with blood glucose fluctuation,which might play a role in the aggravation of diabetic liver injury.
Key wordsBlood glucose    Type 2 diabetes mellitus    Liver injury    Toll-like receptor 4    Tumour necrosis factor-α
收稿日期: 2018-07-30      出版日期: 2019-01-03
ZTFLH:  R587.1  
基金资助:浙江省医药卫生科技计划项目(2015-KY1-001-012); 湖州市科技计划项目(2017GYB11)
通信作者: 钟涛,E-mail:411780188@qq.com   
作者简介: 胡瑜洁,本科,医学检验师,主要从事糖尿病及其并发症的研究工作
引用本文:   
胡瑜洁, 姚晓霖, 钟涛. 血糖波动对糖尿病大鼠肝脏TLR4和TNF-α表达的影响[J]. 预防医学, 2019, 31(1): 15-19.
HU Yu-jie, YAO Xiao-lin, ZHONG Tao. Effects of blood glucose fluctuation on the expression of TLR4 and TNF-α in the liver of diabetic rats. Preventive Medicine, 2019, 31(1): 15-19.
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http://www.zjyfyxzz.com/CN/10.19485/j.cnki.issn2096-5087.2019.01.004      或      http://www.zjyfyxzz.com/CN/Y2019/V31/I1/15
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