Studies On Regulation Effects And Mechanism Of Turochenodeoxycholic Acid Immunologic Function In Mice

Taurochenodeoxycholic Acid(TCDCA)is one of main active components in animal biliary,its chemical name is 3α,7α-dioxy-5β-24-cholane-oyl-N- Taurine, which is an acor-compound combined from Taurine and Chenocholic acid. This topic systematically studied on immunological regulation effects of TCDCA, and intended to approach the immunological regulation effects and mechanism of TCDCA on normal and low immune function mice organisms. Then the main contents include:(1)We detected the effects of TCDCA on mice peritoneal macrophage phagocytosis,peripheral blood IL-1βand IgG contents,spleen IL-2 genetic expression by chicken red blood cell demi-intracorporal method,ELISA method and actual time fluorescent quantitation PCR technique. The experimental results showed: According to 0.1g/kg·b·w , peroral administration of TCDCA can extremely elevate the phagocytosis of mice peritoneal macrophage, and achieve the maximum effective strength; can significantly elevate peripheral blood IL-1βand IgG contents; can elevate spleen IL-2 expressional quantity; according to 0.153g/kg·b·w and 0.189g/kg·b·w , administration of TCDCA all can significantly restrain the phagocytosis of mice peritoneal macrophage, degrade spleen IL-2 expressional quantity; and when TCDCA dosage reach 0.189g/kg·b·w, also can significantly restrain peripheral blood IgG contents. So, indicated that normal organism immunomodulation effect of TCDCA has close relationship with its dosage, and between 0.043～0.1g/kg·b·w, show enhancement property on organism specificity and non-specificity immunologic functions. When dosage is 0.1g/kg·b·w,the effect is most strong and more than 0.1g/kg·b·w, immunifaction begin to weaken, even create the inhibitory action.(2)We also detected the effects of TCDCA and metabolic products CDCA and Tau on culturing in vitro mice peritoneal macrophage and splenic lymphocyte proliferative response,cytokine secretion et al immunological functions by using MTT method,phagocytose neutral red method,ELISA method. The experimental results showed:①When final concentrations were 0.01,1 and 10μg/ml, TCDCA had the prominent enhancement property on normal peritoneal macrophage proliferative response and had the prominent synergistic effect on LPS induced proliferative response. When final concentrations were 0.01,0.05 and 1μg/ml, TCDCA had the prominent enhancement property on peritoneal macrophage excrete IL-1βand when 0.01μg/ml, TCDCA had the prominent synergistic effect on LPS induced peritoneal macrophage excrete IL-1β, and when 1μg/ml, TCDCA had the prominent inhibitory action on LPS irritant peritoneal macrophage excrete IL-1β. TCDCA had un-significant effect on normal peritoneal macrophage phagocytosis.②When final concentrations were 0.1 and 1μg/ml, TCDCA had the prominent enhancement property on splenic lymphocyte proliferative response, and when 0.1μg/ml, TCDCA had the prominent antagonistic effect on ConA irritant proliferative response. TCDCA had un-significant effect on all LPS and CsA irritant splenic lymphocyte proliferative response. When final concentrations was 0.01μg/ml, TCDCA had the prominent enhancement property on splenic lymphocyte excrete IL-2, and TCDCA had un-significant effect on ConA irritant splenic lymphocyte excrete IL-2. When final concentrations was 0.01μg/ml, TCDCA had the prominent synergistic effect on LPS induced splenic lymphocyte excrete IL-2, and when 0.05μg/ml, TCDCA had the prominent antagonistic effect on LPS induced splenic lymphocyte excrete IL-2, When 0.01μg/ml, TCDCA had the prominent coordinate repression on CsA inhibitive splenic lymphocyte excrete IL-2. When final concentrations were 0.01 and 0.05μg/ml, TCDCA had the prominent enhancement property on splenic lymphocyte excrete IgG, and when 0.05 and 0.1μg/ml, TCDCA had the prominent synergistic effect on LPS induced splenic lymphocyte excrete IgG.③When final concentrations were 0.5 and 5μg/ml, CDCA and Tau had un-significant effects on all normal and suboptimal dose LPS irritant peritoneal macrophage,splenic lymphocyte proliferative response and splenic lymphocyte excrete IgG, but had the prominent enhancement property on normal peritoneal macrophage excrete IL-1β.When final concentration was 5μg/ml, CDCA had the prominent enhancement property on peritoneal macrophage phagocytosis and Tau had the prominent inhibitory action on peritoneal macrophage phagocytosis. When final concentration was 0.5μg/ml, CDCA had the prominent enhancement property on normal splenic lymphocyte excrete IL-2. When final concentrations were 0.5 and 5μg/ml, Tau had the prominent or extremely prominent enhancement property on either normal or ConA,LPS irritant splenic lymphocyte excrete IL-2 and when 0.5μg/ml, Tau had the prominent reablement effect on CsA inhibitive IL-2 excreting.(3)We evaluated the effects of TCDCA on CTX and CsA prepared lower nonspecific and specific immunological function mice model. The results showed: According to 0.1g/kg·b·w , peroral administration of TCDCA had the prominent enhancement or reablement effects all on lower nonspecific immunity function model mice peritoneal macrophage phagocytosis and lower specific immunity function model mice peripheral blood IgG.(4) We analyzed the vivo metabolism control lattice of TCDCA, predicted effects of this medicine on nerves-endocrine-immunomodulation system, moreover, detected the contents of hydrocortisone in post- administration mice blood serum by utilizing radio-immunity method. The results showed: According to 0.1g/kg·b·w , peroral administration of TCDCA had the extremely prominent enhancement property on hydrocortisone contents in mice neuro- humor-immunomodulation system.These chief conclusions below are yielded from this experimental study:(1)The optimization dosage of TCDCA on enhancing mice immunologic function is 0.1g/kg.(2)Either on nonspecific immunity function or specific cellular immunity,humoral immune function of mice organism, TCDCA all showed the prominent dose dependent two-way immunomodulation effect.(3)Either on normal mice organism or low immunologic function mice, TCDCA all had evident immunomodulation effects.(4)The regulation effect of TCDCA on mice organism immunological function is the results of TCDCA and its metabolites CDCA and Tau directly affect together on immunocell and produce influence on organism neuro-humor-immunomodulation system.