| Lipid metabolism is one of the most important metabolic systems in organism. The disorder of lipid metabolism included the abnormal serum lipid level and the abnormal aggregation of lipid in tissues. Epidemiological studies have shown the close correlation between the disorder of lipid metabolism and many severe diseases, including stroke, atherosclerosis, diabetes and so on. In traditional views, the disorder of lipid metabolism was mostly considered as a genetic disease, and was affected by living habits partially. However, it was found that persistent inflammation caused by Zymosan could induce the aggravation of serum lipid disorder in our recently studies, which implied that persistent inflammation might play an important role in lipid metabolism process. Meanwhile, the disorder of serum lipid level occurred in patients with chronic inflammation disease, such as rheumatic arthritis and lupus erythematosus. Besides the serum lipid level, the abnormal aggregation of lipid in tissues was a health care problem yet. Among that, the lipid aggregation under endarterium was the most danger one, because it would induce atherosclerosis. And the key point of atherosclerosis progression was the formation of foam cell. Therefore, this study was designed to explore the action of persistent inflammation in lipid metabolism in vivo and in vitro.Panax notoginseng saponins (PNS) are the principal ingredient extracted from the traditional Chinese herb Panax notoginseng and have extent effects on lipid metabolism and cardiovascular diseases. IH 901 is the metabolized product of the PNS by intestinal bacteria in human and rat,which was regarded as the main effective monomer of metabolized Ginsenosides in vivo. Effects of PNS and IH901 were also observed in this study.Methods1. To observe the action of persistent inflammation on lipid metabolism in hyper-fat diet rats, animals were divided into four groups including hyper-fat diet group (high fat diet), inflammation group (high fat diet + zymosan, 20 mg/kg, i.p., once every 5 days), PDTC group (high fat diet +zymosan, 20 mg/kg, i.p., once every 5 days + PDTC, 100 mg/kg, i.p., daily) and PNS group (high fat diet + zymosan, 20 mg/kg, i.p., once every 5 days + PNS 120 mg/kg, i.g., daily).2. To study the effect of persistent inflammation on lipid metabolism in normal rats, animals were divided into four groups including control group (normal diet), simple-inflammation group (normal diet + zymosan, 20 mg/kg, i.p., once every 5 days), PDTC group (normal diet + zymosan, 20 mg/kg, i.p., once every 5 days + PDTC, 100 mg/kg, i.p., daily) and PNS group (normal diet + zymosan, 20 mg/kg, i.p., once every 5 days + PNS 120 mg/kg, i.g., daily).3. To explore the action of inflammation on the formation of foam cell, cells were divided into four groups as control, inflammation group, PDTC group and IH901 group. Rat's peritoneal macrophages were incubated with ox-LDL for 48h as foam cell group. LPS (20mg/L) was added into the medium as inflammation stimuli in inflammation group. Besides LPS, PDTC (25μM) and IH901 (25μM) were given in PDTC and IH901 groups respectively.4. TNF-αlevel was measured with ELISA technique.5. The foam cells were stained by oil red-O after immobilization.6. The level of TG, LDL, HDL, TC, CE and LPL activity were measured using commercial kits.7. The expression of HMG-CoA reductase, PPARα/γ, CD36, ABCA1, PPARγand LXR mRNA were measured by RT-PCR.8. The protein level of LPL, perilipin and NF-κB were measured with western blotting.Results1. Persistent inflammation could induce and aggravate the lipid metabolism disorder in normal rats and hyper-fat diet rats respectively. Compared with control group and hyper-fat diet group, the serum TNF-α, TC, TG and LDL levels increased significantly, and the level of HDL decreased noticeably.2. Persistent inflammation reduced the LPL activity, the expression of LPL and its mRNA, PPARα/γmRNA and up-regulated the expression of HMG-CoA reductase significantly.3. In PDTC and PDTC therapy group, the levels of TNF-α, TC, TG, LDL, the expression of HMG-CoA reductase were decreased and the HDL level, the expression of PPARα/γmRNA, LPL (mRNA and protein), the activity of LPL were increased by comparison of that in inflammation group and simple-inflammation group respectively.4. The treatment of PNS (i.g.) could improve the lipid metabolism disorder caused by inflammation. In PNS and PNS therapy group, the levels of TNF-α, TC, TG, LDL, the expression of HMG-CoA reductase were decreased and the HDL level, the expression of PPARα/γmRNA, LPL (mRNA and protein), the activity of LPL were increased by comparison of that in inflammation group and simple-inflammation group respectively.5. The inflammation could increase the lipid aggregation in foam cells. The levels of TC, CE, CE/TC ratio and TNF-αincreased significantly compared with foam cell group.6. Inflammation reduced the expression of CD36, ABCA1, PPARγand LXR mRNA and increased the expression of perilipin (mRNA and protein) significantly.7. The treatment of PDTC could up-regulate the expression of CD36, ABCA1, PPARγand LXR mRNA and down-regulate the expression of perilipin (mRNA and protein) significantly.8. The treatment of IH901 could up-regulate the expression of ABCA1, PPARγand LXR mRNA and down-regulate the expression of CD36 mRNA, perilipin (mRNA and protein) noticeably. The levels of TC, CE, CE/TC ratio and TNF-αdecreased significantly compared withinflammation group.Conclusion1. Persistent inflammation could induce and aggravate serum lipid metabolism disorder in rats through down-regulating the expression of LPL and up-regulated the expression of HMG-CoA reductase. PPARα/γwere involved in the mechanism of that.2. Inflammation could increase lipid aggregation in foam cells in vitro, which might be related with the increased expression of perilipin and the decreased expression of ABCA1.3. The treatment of PNS could ameliorate the lipid metabolism disorder induced by persistent inflammation via up-regulating the expression of LPL and down-regulated the expression of HMG-CoA reductase. 4. The metabolite monomer of PNS, IH901 could reduce the excessive lipid aggregation in foam cells caused by inflammation stimulation. The mechanism might be related with the decreased expression of perilipin, the increased expression of ABCA1 and the decreased expression of CD36.
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