Experimental And Chlinical Studies On Treating Ulcerous Colitis Of Jiuxieling Granules

OBJECTIVES:This study is to investigate experimental effects of JXLG on lipid peroxidation levels, inflammatory cytokines levels, pathological change,expressions of NF-κB and ICAM-1 of colon in model with rats UC established by immune method combined with local stimulation of acetic acid, and to observe clinical effects and colon mucosa indexes of IgA, IgG, IgM and Complement C3 of JXLG on 32 patients with UC, so as to explore the effects of JXLG on the prevention and treatment of UC and its pharmacological mechanisms invovled.METHODS:1. To establish UC model by immune method combined with local stimulation of acetic acid. Wistar rats were randomly divided into six groups as follows:normal control group, model group, positive group, low,middle and high dosage of JXLG groups. Rats in positive control group were treated with SASP, and those in three treatment groups were treated with low,middle and high dosage of JXLG respectively for 14 days continuously.24 hours after last administration, the rats were killed to obtain colon mucous membrane and blood serum. Both the homogenate of colon mucous membrane concentration and blood serum concentration of IL-4 and TNF-a were measured by RIA, and the blood serum concentration of IFN-γwas measured by ELISA. The homogenate of colon mucous membrane were made to determine GSH-Px,SOD,MDA,NO,TNOS and iNOS concentration by biochemistry method. In addition, colon mucous membrane was made biopsy through HE staining to calculate histopathological score. And immunohistochemical sections were made to research expressions of NF-κB and ICAM-1 in colon tissue.2.64 patients were randomly divided into treatment group and control group, treatment group was treated with JXLG by oral and enema treatment, and the control group was treated with SASP. Both groups were treated 3 continuous courses as a whole course, and each course lasts 2 weeks. After treatment, the total efficiency, colon lesions, IgA, IgG, IgM and complement C3 changes of pre-treatment and post-treatment were observed to compare and analyze the effects of JXLG.RESULTS:1. JXLG could markedly improve colon mucosal inflammation and decrease histopathological score. The colon mucous of model group suffered different levels of mucosa congestion, edema, ulceration, bleeding and small shallow ulcers with exudative necrotic ulcer expansion around the gland, In addition, the colon mucous glandular epithelial cells became mild hyperplasia, submucosal lamina propria also suffered congestion and edema, and bowel wall layers were filled with inflammatory cells, especially neutrophils. Histopathological scores of model group were significantly higher than that of the normal group (P<0.001). the colon mucous ulcer of JXLG-treated group and SASP group is more superficial, and epithelium adjacent to ulcer repaired significantly, the gland next to ulcer became hyperplasia actively. In addition, the colon mucosal hyperemia, edema and erosion significantly ameliorated, and fewer inflammatory cells infiltrated. Histopathological scores of JXLG-treated groups decreased greatly(P<0.05 or P< 0.001).2. Different doses of JXLG could weaken expressions of NF-κB and ICAM-1 in Colon tissue. The expression of NF-κB of colon mucous in normal group only is weak, but that of model group was slightly higher (P<0.001). The expression of NF-κB of colon mucous in positive control group and JXLG-treated groups reduced(P<0.01 or P<0.05). The expression of ICAM-1 of colon mucous in normal group is weak, but that of model group was significantly higher than the normal group and JXLG-treated groups (P<0.01).3. JXLG could markedly increase the levels of GSH-Px,SOD, while decrease the levels of MDA, NO, TNOS and iNOS. Compare with normal control group, the MDA, NO, TNOS and iNOS levels of colon mucous membrane of model group increased (P <0.01), and the SOD and GSH-Px levels of colon mucous membrane of model group decreased markedly (P<0.01), the results indicated that complex UC models were made successfully. Compare with model group, the SOD and GSH-Px concentration of high and middle dosage group of JXLG increased markedly(P<0.01 or P<0.05), and the MDA, NO, TNOS and iNOS levels of colon mucous membrane in the same group decreased markedly (P<0.01). the NO, TNOS and iNOS levels of colon mucous membrane in the high and middle dosage group of JXLG decreased markedly (P<0.001 or P<0.05), and the effects of the high dosage group of JXLG particular functioned further.4. The content of IFN-y in blood serum of model group was higher than that of normal group(P<0.01); and the contents of IFN-y in blood serum for three JXLG-treated groups were lower than that of model group(P<0.01 or P<0.05). The content of IL-4 in blood serum for model group was lower than that of normal group(P<0.01); and the contents of IL-4 in blood serum for middle and high dosage of JXLG-treated groups were higher than that of model group(P<0.01 or P<0.05). The content of TNF-a in blood serum fro model group was higher than that of normal group(P< 0.01);and the contents of TNF-a in blood serum for middle and high dosage of JXLG-treated groups were lower than that of model group(P< 0.01 or P<0.05). The homogenate of colon mucous membrane content of IL-4 of model group was lower than that of normal group(P< 0.01); and the homogenate of colon mucous membrane contents of IL-4 in all three JXLG-treated groups were higher than that of model group(P<0.01 or P<0.05). The homogenate of colon mucous membrane content of TNF-a in model group was higher than that of normal group(P <0.05); and the homogenate of colon mucous membrane content of TNF-a in all three JXLG-treated groups were lower than that of model group(P<0.01 or P< 0.05).5. JXLG can significantly improve the clinical symptoms, and improve the body's immunity and resistance, and reduce the levels of IgA, IgG, IgM and complement. C3 The total effective rate in treatment group was 90.6%, while 78.1% in control group.CONCLUSIONS:1. JXLG has a significant intervention effect on rat model of UC, which may be act as an antioxidant of resisting free radical damage and inhibiting of NO, TNOS and iNOS production, enhance antioxidant enzyme activity. and increase the level of IL-4, decrease that of IFN-γand TNF-a. JXLG also could block inflammation and reduce the amplification effect of colon inflammation by inhibiting activation of NF-κB and expression of ICAM-1, So JXLG have a better therapeutic effect on UC, and which is an effective traditional Chinese medicine granules of treatment on UC.2. JXLG has the better effects on treating UC. JXLG could improve the body's immunity and strengthen capacity to regulate colon disorders.