Effects Of Triglyceride On Tissue Steatosis Of SD Rats And On Bidirectional Proliferation Of A7r5 Cells

Triglyceride is a fat molecule composed of 3 molecules of fatty acids and 1 molecule of glycerol,which is the most abundant lipid in the human body.Most of tissues can metabolize TG to obtain energy.Previous studies have shown that plasma TG is involved in the migration and proliferation of vascular smooth muscle cells(VSMCs),affecting the balance between proliferation and apoptosis of VSMCs,and involved in the development of atherosclerosis(AS).In the first part,Sprague-Dawley rat modle of hyperlipidemia induced by intraperitoneal injection of poloxamer 407(P-407)were used to explore the relationship between serum TG and tissue degeneration.In the second part,the effects of TG on the proliferation of A7r5 cells and its molecular mechanism were explored.The results are as follows:(1)Compared with saline group,the concentrations of serum TG,TC,HDL and LDL were significantly increased in P-407 group.(2)There was fatty degeneration in the liver,kidney and spleen of P-407 group,which was time-dependent.(3)Spearman non-parametric correlation analysis showed that the tissue steatosis was positively correlated with atherogenic index of plasma(AIP)and TC / HDL ratio(all p < 0.001).(4)Compared with the saline group,the weight of the animals was significantly reduced after 3 or 4 months of treatment with P-407.(5)Within a certain concentration range,oleic acid and palmitic acid can bidirectional regulation on proliferation of A7r5 cells,that is,low concentration promotes proliferation,and high concentration inhibits proliferation.Glycerin has a one-way promotion of A7r5 cell proliferation.(6)After selective blockade of HGF/cMET signaling pathway by PHA 665752,the effect of oleic acid on cell proliferation was blocked.There was no significant difference in cell proliferation rate between the DMSO group and three doses of oleic acid group 0.005 mg/dL,0.05 mg/dL and 1 mg/dL(containing 2 ?M PHA 665752),respectively.(7)The results of ELISA test showed that,compared with the control group,the expression of HGF in the cell supernatant was increased in the low-concentration oleic acid group(0.005 mg/dL to 1 mg/dL)and was decreased in the high-concentration oleic acid group(5 mg/dL and 20 mg/dL).(8)The results of Western Blot showed that,compared with the control group,the expression of HGF was increased in low concentration of oleic acid(0.005 mg/dL and 1 mg/dL)groups and was reduced in high concentration of oleic acid(20 mg/dL)group.The findings are as follows:(1)Intraperitoneal injection of P-407 can cause elevated blood lipids in SD rats,and the increase of TG concentration is most significant.(2)the fatty degeneration in the liver,kidney and spleen can be induced by high levels of TG,and the longer the P-407 treatment time,the more serious the degree of tissue steatosis.(3)Oleic acid and palmitic acid can bidirectional regulating the proliferation of A7r5 cells,and glycerol can only promote the proliferation of A7r5 cells.(4)Oleic acid may exert its bidirectional regulation of A7r5 cells proliferation by affecting the HGF/cMET signaling pathway.