[Protection of huanglian jiedu decoction on systemic and vascular immune responses of high fat induced apoE(-/-) mice].
OBJECTIVE
To observe the effect of Huanglian Jiedu IJecoction (HJU) on systemic and vascular immune responses of high fat diet fed apoE deficient (apoE(-/-)) mice.


METHODS
Eight wild type C57BL6 mice were recruited as the wild type common food group. Totally 24 apoE(-/-) mice were randomly divided into the ApoE'common food group, the ApoE(-/-) hyperlipidemia group, and the ApoE(-/-) hyperlipidemia plus HJD group, 8 in each group. In the present study, the common food mice and high fat fed mice were fed with a chow diet or a high cholesterol diet for 4 weeks. HJD was given to mice in the ApoE(-/-) hyperlipidemia plus HJD group at the daily dose of 5 g/kg by gastrogavage, while equal volume of pure water was given to mice in the rest groups by gastrogavage. Four weeks later, the plasma levels of blood lipids, the ratio of peripheral blood mononuclear cells, and expressions of Toll-like receptor 4 (TLR-4) and CD36 on the monocytes were detected. The pathological changes and expressions of cytokines in local aorta were detected. The plasma cytokine levels in response to lipopolysaccharide (LPS) were analyzed. Results (1) Compared with the wild type common food group, TO, TG, and LDL-O significantly increased in the ApoE(-/-) common food group (P < 0. 05, P < 0.01). Compared with the ApoE(-/-) common food group, TC and LDL-C significantly increased in the hyperlipidemia group (P < 0. 05). There was no statistical difference in each index between the ApoE(-/-) hyperlipidemia group and the ApoE(-/-) hyperlipidemia plus HJD group (P > 0.05). (2) Compared with the wild type common food group, no obvious change of the ratio of peripheral blood mononuclear cells happened, the TLR4 expression level significantly increased in the ApoE'common food group (P < 0. 05). Compared with the ApoE common food group, the ratio of peripheral blood mononuclear cells and the TLR4 expression level significantly increased in the ApoE' hyperlipidemia group (P < 0.05). Compared with the ApoE(-/-) hyperlipidemia group, the ratio of peripheral blood mononuclear cells and the TLR4 expression level significantly decreased. Besides, the CD36 expression level also significantly decreased (P<0.05). (3) After stimulated by LPS for 3 h, compared with the wild type common food group, plasma TNF-ct and IL-b expressions significantly increased in the ApoE(-/-) common food group (P < 0.05). Compared with the ApoE(-/-) common food group, plasma expressions of IL-12, TNF-alpha, MCP-1, and IL-10 increased, but with no statistical difference in the ApoE(-/-) hyperlipidemia group (P > 0.05). After 4-week intervention of HJD, compared with the ApoE(-/-) hyperlipidemia group, the MCP-1 expression was significantly down-regulated, while the IL-10 expression significantly increased, showing statistical difference (P < 0.05). Compared with the wild type common food group, mRNA expression levels of IFN-gamma, MCP-1 , TNF-alpha, IL-10, and IL-1beta significantly increased (P < 0. 05, P < 0.01). Compared with the ApoE(-/-) common food group, not only mRNA expression levels of IFN-gamma, MCP-1, TNF-alpha, and IL-1beta, further significantly increased, but also IL-12, IL-10, and TGF-beta significantly increased (P < 0. 05, P < 0. 01). After 4-week intervention of HJD, compared with the ApoE(-/-) hyperlipidemia group, mRNA expression levels of MCP-1, TNF-alpha, IL-1beta, and IL-12 significantly decreased in the ApoE(-/-) hyperlipidemia plus HJD group (P < 0.05, P < 0.01).


CONCLUSIONS
High fat diet induced systemic reaction and inflammatory reactions of local vessels. The local inflammatory response of vessels exceeded systemic inflammatory response. Intervention of HJD could attenuate inflammatory response, especially in local arteries. Meanwhile, it enhanced systemic anti-inflammatory reactions.
Lab for Molecular Biology, Institute of Basic Theory on Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing (100700), China.
Ya-luan
YL
Ma
Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing (100011), China.
Bei-bei
BB
Wang
Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing (100011), China.
Jun-yan
JY
Han
Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing (100011), China.
Rui
R
Li
Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing (100011), China.
Wei-mei
WM
Zhang
Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing (100011), China.
Tong
T
Li
Lab for Molecular Biology, Institute of Basic Theory on Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing (100700), China.
Bing
B
Chen
Lab for Molecular Biology, Institute of Basic Theory on Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing (100700), China.
Jing
J
Su
Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing (100011), China.
Xian-bo
XB
Wang
Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing (100011), China.
Hui
H
Zeng
D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D018955:CD36 Antigens / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D006949:Hyperlipidemias / Q000097:blood / Q000209:etiology / Q000276:immunology*; D007249:Inflammation; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000209:etiology / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D001057:Apolipoproteins E; D018955:CD36 Antigens; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004041:Dietary Fats; D004365:Drugs, Chinese Herbal; C556062:IL10 protein, mouse; D053583:Interleukin-1beta; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C494417:huanglian; D016753:Interleukin-10; D018664:Interleukin-12