Comparative Research on the Effects of Huanglian Jiedu Tang and Lipid-Lowering Drugs on the Innate Immune Response of ApoE-/-mice
Objective To compare the effects of Huanglian Jiedu Tang,Atorvastatin,Fenofibrate and Rosiglitazone on the systemic and aortic local immune responses in ApoE knockout(ApoE-/-)mice with western diet(WD).Methods 60 female 8-week-old ApoE-/-mice were randomly divided into control group,model group,atorvastatin group,fenofibrate group,rosiglitazone group,and Huanglian Jiedu Tang group using paired comparison method.10 matched C57BL/6J mice were used as wild control group.The control group and wild control group were feed chow diet,the model group was feed WD,and the treatment groups were feed WD at the same time with atorvastatin(3 mg/kg),fenofibrate(33 mg/kg),rosiglitazone(0.67 mg/kg),and Huanglian Jiedu Tang(5 g/kg).After 4 weeks,half of mice in each group were sacrificed,the blood lipid level,the proportion of monocytes and their receptors toll-like receptor 4(TLR4)and CD36,and the subtypes of monocyte in peripheral blood were detected by flow cytometry.The pathogenesis of aorta was detected by HE staining,and inflammatory cytokines in aorta were detected by RT-qPCR.The rest of mice were stimulated by lipopolysaccharide(LPS),then the serum cytokines were detected by ELISA and cytometric bead array(CBA).Results Compared with the wild control group,the levels of total cholesterol(TC),triglyceride(TG),and low density lipoprotein(LDL)in the plasma of the control group mice were significantly increased(P＜0.01),while the levels of high density lipoprotein(HDL)were significantly reduced(P＜0.01).The proportion of Ly6C++in the peripheral blood increased(P＜0.05),while the proportion of Ly6C-and Ly6C+decreased(P＜0.05).The expression of interleukin(IL)-6,IL-12,tumor necrosis factor(TNF)-α,monocyte chemotactic protein(MCP)-1,and nitric oxide synthase(NOS)-2 in aortic tissue increased(P＜0.05).After LPS stimulation,the plasma levels of IL-6 and TNF-α increased(P＜0.05).Compared with the control group,the levels of TC,TG,HDL,and LDL in the model group mice further increased(P＜0.05).The proportion of monocytes increased(P＜0.05),and the expression level of CD36 increased(P＜0.05).The mRNA expression of IL-1β,IL-12,TNF-α,and NOS-2 in aortic tissue increased(P＜0.05).The plasma levels of IL-1β,IL-12 p70,and MCP-1 increased after LPS stimulation(P＜0.05).Compared with the model group,atorvastatin intervention did not decreased lipid levels(P＞0.05),but reduced the mRNA expression of IL-1β,IL-6,IL-12,TNF-α,MCP-1,and NOS-2 in aortic tissue(P＜0.05).Fenofibrate reduced HDL levels(P＜0.01),but decreased the mRNA expression of IL-12,TNF-α,MCP-1,and NOS-2 in aortic tissue(P＜0.05).Rosiglitazone did not reduced lipid levels(P＞0.05),but decreased the proportion of Ly6C++in blood(P＜0.05);and reduced the mRNA expression of IL-1β,IL-6,IL-12,TNF-α,and NOS-2 in aortic tissue(P＜0.05).After LPS stimulation,rosiglitazone reduced plasma IL-12 p70 levels(P＜0.05).The intervention of Huanglian Jiedu Tang did not significantly regulated lipid levels(P＞0.05),but significantly reduced the proportion of monocytes and their subtypes Ly6C++(P＜0.05),decreased the expression levels of TLR4 and CD36 of monocytes(P＜0.05),and reduced the mRNA expression of IL-1β,IL-12,and NOS-2 in aortic tissue(P＜0.05).Conclusion Huanglian Jiedu Tang,Atorvastatin,Fenofibrate and Rosiglitazone can respectively modulate innate immune disproportions in a lipids-lower-independent manner.Among them,Huanglian Jiedu Tang and Rosiglitazone have more significant effects on regulating systemic inflammatory immunity than Atorvastatin and Fenofibrate.
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