Experimental Studies On The Antagonistic Effect Of Taurochenodeoxycholic Acid On The Side Effect Induced By Glucocorticoid

Glucocorticoid is used extensive for its many pharmacologic actions. But it has been shown that patients treated with glucocorticoids have the side effect of immune suppression, intestinal mucosa injury, adrenopause and osteoporosis. No effective drug to protect the patients from side effect of glucocorticoids has been discovered so far aboard. So novel methods and drugs to relieve the side effect of glucocorticoids are an important mission for clinic medicine and still remained to be found. 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 the antagonistic effect ofTaurochenodeoxycholic Acid on the side effect induced by Glucocorticoid, and intended to approach the antagonistic effects of TCDCA on mice organisms. The experimental model of the mice was build with dexamethasone, three doses of TCDCA were intragastriced to the mice, including 0.05, 0.1 and 0.2g/kg.Then the main contents include:(1) The effect of TCDCA on the immunosuppression mice with glucocorticoid. The weight of the immune organs were measured, the phagocytosis of the mononuclear phagocyte system was determined by using Carbon particle clearance test, the valence of CD4+, CD8 +in the blood cell and CD4+/CD8+ value were measured by using Flow cytometry and the content of IgG in serum was assayed by using ELISA. Compared with the control group, three doses of TCDCA could significantly increase the index thymus and spleen (P<0.01); 0.05 and 0.1g/kg doses groups could significantly improve the phagocytic function of the mononuclear phagocyte system(P<0.01); three doses of TCDCA could enhanced the percentage of CD4+ lymphocytes(P<0.05) and 0.1g/kg dose group could increase CD4+/CD8+ value in peripheral blood(P<0.05); the content of serum IgG in mice was enhanced by 0.05 and 0.1g/kg doses groups (P<0.05). TCDCA can significantly enhance the immune function of the immunosuppression mice with Glucocorticoid.(2) The effect of TCDCA on intestinal mucosa injury induced by glucocorticoid.Voluntary feed intake of the mouse were measured; the content of sIgA in intestinal tract were tested by using RIA; the expressions of caspase-3 mRNA were measured by using RT-PCR; EdU-based S-phase assay was employed to display proliferation cells in small intestine; the intestine was observed through paraffin section, hematoxylin and eosin stain (HE). Compared with the control group, 0.1g/kg dose group could significantly improve the voluntary feed intake (P<0.01); the content of SIgA was enhanced by 0.05 and 0.2g/kg dose group (P<0.05) and was significantly enhanced by 0.1g/kg dose group (P<0.01); the expressions of caspase-3 mRNA of the 0.1g/kg dose group was only 50% of that in Control; the cell proliferation index was significantly improved by 0.1g/kg dose group (P<0.01); pathomorphological examination showed that the pathological change of the 0.1g/kg dose group was obviously better than the Control. TCDCA can protect intestinal mucosa injury induced by glucocorticoid.(3) The effect of TCDCA on adrenopause induced by glucocorticoid.The content of corticosterone in blood serum were tested by using ELISA; the loaded swimming time was observed; EdU-based S-phase assay was employed to display proliferation cells in adrenal cortex; the adrenal cortex was observed through paraffin section, hematoxylin and eosin stain (HE); the apoptosis in adrenal cortex was employed though TUNEL. Compared with the control group, the content of corticosterone was enhanced by 0.1g/kg dose group (P<0.05); the loaded swimming time was prolonged by 0.1g/kg dose group (P<0.05) and was significantly enhanced by 0.2g/kg dose group (P<0.01); the cell proliferation index was significantly improved by 0.1g/kg dose group (P<0.01); the cell Apoptotic index was significantly reduced by 0.1g/kg dose group (P<0.01); pathomorphological examination showed that the pathological change of the 0.1g/kg dose group was obviously better than the Control. TCDCA can protect adrenopause induced by glucocorticoid.(4) The effect of TCDCA on the Secondary Osteoporosis induced by glucocorticoid.Serum calcium, serum phosphorus and serum alkaline phosphatase were measured by using Automatic bio-Chemical Analysis Instrument; serum osteocalcin were tested by using RIA; radiographic analysis was performed to study the bone density using the ImageJ software. Compared with the control group, three doses of TCDCA could significantly increase the content of serum alkaline phosphatase (P<0.01); three doses of TCDCA could enhanced the content of serum calcium and serum phosphorus(P>0.05); three doses of TCDCA could significantly increase the content of serum osteocalcin (P<0.01); Radiographic measurement showed that three doses of TCDCA could significantly increase the bone density(P<0.01). TCDCA can significantly enhance the bone density of the osteoporosis mice and have a good effect on the secondary osteoporosis induced by glucocorticoid.These chief conclusions below are yielded from this experimental study:Either on immune suppression or intestinal mucosa injury, adrenopause, osteoporosis of mice organism induced by glucocorticoid, TCDCA all showed the available antagonistic effect.