Effects of blood glucose fluctuation on the expression of TLR4 and TNF-α in the liver of diabetic rats / 预防医学

ABSTRACT

Objective@# 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.