Efects Of Huanglian Zhuyu Decoction On LPS–TLR4-NF-?B Network And Inflammatory Factors In Rats With Metabolic Syndrome

Objective:In this study,huanglian zhuyu decoction(HZ)was selected to intervene in rats with metabolic syndrome(MS),and the effect of HZ on body weight,fasting insulin(FINS),fasting blood glucose(FBG),blood lipid,hemorrheology and liver tissues of MS rats was studied to verify the effectiveness of HZ in MS rats.By studying the effect of HZ on the changes of liposolysaccharide(LPS),tumor necrosis factor-?(TNF-?),interleukin-6(IL-6)levels in serum and the expression of toll-like receptor 4(TLR4)and nuclear transcription factor-?B(NF-?B)in the liver of MS rats,we investigated whether HZ regulated the LPS-TLR4-NF-?B network to reduce the effect of IR treatment on MS.It provides a new research idea and experimental basis for the treatment of MS with Chinese medicine compound.At the same time,the dose-effect relationship between different doses was evaluated,which laid a foundation for the further development of effective new drugs for the treatment of MS.Methods:MS rat model was prepared by high-sugar and high-fat diet combined with streptozotocin(STZ)injection.Rats were divided into control group,model group,low HZ group,high HZ group and western medicine group.The low HZ group was fed with10g/kg·d,the high HZ group with 20g/kg·d,and the western medicine group with200mg/kg· metformin +4mg/kg·d atorvastatin calcium.Weekly record of rat body weight,record every 2 weeks rats FBG,4 weeks after drug treatment,blood and liver samples used to test blood lipid,FBG,hemorrheology in item 4 by using enzyme-linked immunosorbent(ELISA)to detect the FINS,LPS and TNF-? and IL-6,using Western blot method detecting TLR4 in the liver,the NF-?B p65 protein expression and HE staining to observe the liver pathological change.Results:(1)It was found that the weight of the three treatment groups decreased significantly before and after treatment(P<0.05).In terms of improving FBG,FINS level,IR and liver coefficient,all the 3 treatment groups showed efficacy,which was significantly different from the model group(P<0.05),but there was no significant difference among the 3 treatment groups.In terms of blood lipids,the treatment group was significantly improved compared with the model group(P<0.05).The therapeutic effect of the two groups was significantly better than that of the Western medicine group(P<0.05),and the therapeutic effect of the high HZ group was significantly better than that of the low group(P<0.05).In terms of the improvement of hemorheology,the treatment group of the3 groups was significantly improved compared with the model group(P<0.05),the treatment group with high HZ was significantly more effective than the other 2 groups(P<0.05),and the treatment group with low HZ had the same effect as the Western medicine group.(2)It was found that the three treatment groups were effective in reducing serum LPS and inflammatory factors,which were significantly different from the model group(P<0.05).In terms of reducing LPS and TNF-?,the efficacy of the high HZ group was significantly higher than that of the low HZ group(P<0.05),but the efficacy of the low HZ group was comparable to that of the Western medicine group.There was no significant difference in the efficacy of IL-6 reduction among the 3 treatment groups.In terms of the improvement of liver pathology,the treatment group of the three groups could reduce the steatosis and inflammatory infiltration of hepatocytes and increase the number of normal cells,and the improvement of the group with high HZ was more obvious than that of the other two groups,while there was no significant difference between the group with low HZ and the western medicine group.(3)It was found that TLR4 and NF-?B p65 protein expression in the liver of the three treatment groups were significantly reduced compared with the model group(P<0.05).The TLR4 protein expression in the two groups of TCM was significantly lower than that in the Western medicine group(P<0.05),and the therapeutic effect of the high HZ group was significantly lower than that of the low group(P<0.05).However,in terms of reduction of NF-?B P65,the treatment group with low HZ was significantly more effective than the other two groups(P<0.05),while there was no difference between the high HZ group and the western medicine group.Conclusion:(1)STZ injection on a high-sugar and high-fat diet is one of the methods for the preparation of MS rat model.(2)HZ can improve the blood lipid of MS rats,and the efficacy is more significant than that of western drugs and increases with the increase of dose.HZ can improve the liver pathology and hemorheology of MS rats.The effect of high dose is less obvious thanthat of low dose and western medicine,but the effect of low dose is no different from that of western medicine.HZ can improve weight,liver coefficient,blood glucose,insulin and IR in MS rats.(3)It was speculated that the mechanism of action of HZ in the treatment of MS might be to inhibit the activation of TLR4 and NF-?B in the liver by reducing the level of serum LPS,thereby reducing the release of TNF-? and IL-6 and improving IR.