Establishment Of Diabetes Mellitus Combined With Syphilis Model In Rabbits And Analysis Of Tissue Damage And The Pathogenesis

Objective: To construct animal model of diabetes mellitus combined with syphilis, Dynamic monitoring function change of liver and kidney, Detect the pathological and physiological changes of heart, lungs, liver, kidney tissues and the expression level of thioredoxin interacting protein(TXNIP) in kidney, for further research on the molecular mechanism of TXNIP in the renal injury and provide experiment basis for treatment of diabetes mellitus combined with syphilis.Methods: 1. Establish animal model : 29 male New Zealand rabbits were divided into four groups after one week of adaptability feeding. Five rabbits of control group(group C) were fed conventionally. Eight rabbits of diabetes group(group DM) were established by injecting of 100 mg/kg alloxan by ear vein; Eight rabbits of Syphilis group(group Tp) were established by vacciating Treponema pallidum(T.pallidum) to testicular; Eight rabbits of the diabetes mellitus combined with syphilis(group H) group were established by injecting alloxan firstly, then vacciating T.pallidum. Successful standards of diabetes model is fasting blood glucose > 16.0mmol/L continuously, Criteria of syphilis modeling is silver staining of T. pallidum positive and TPPA positive.2. Determination of biochemical indicetes: Collecting blood from ear once two weeks when the models were stabled, change of serum fasting blood glucose(FBG), fasting insulin(INS), serum albumin(ALB), alanine aminotransferase(ALT), urea nitrogen( BUN), creatinine(Cr) were observed.3. Pathological examination: Tissues of rabbit heart, lung, liver, kidney were collected for Pathologic biopsy, HE staining and immunohistochemistry of renal tissue, then the pathological changes of each organization were observed and expression of TXNIP in the kidney were detected.Results:1. Diabetic rabbit models were successfully established by injecting alloxan, standards of diabetes model is fasting blood glucose > 16.0mmol/L continuously; T. pallidum Nichols strains were recovered successfully, then syphilis rabbit models were successfully infected, criteria of syphilis modeling is silver staining of T.pallidum positive and TPPA positive; The diabetes mellitus combined with syphilis rabbit models were successfully established by injecting alloxan firstly, then vacciating T.pallidum, criteria of the diabetes mellitus combined with syphilis rabbit model is fasting blood glucose > 16.0mmol/L, meanwhile silver staining of T.pallidum positive and TPPA positive.2. Blood glucose of group DM and group H were significantly higher, meanwhile the insulin of group DM and group H were decreased obviously. Compared with group DM, group H has no statistical significance(P>0.05). Since 8 weeks, the BUN, Cr and ALT in group H rabbits were increased significantly, while ALB was significantly lower, compared with group Tp and group DM, group H has statistical significance(P<0.05).3. Compared with the control group, the experimental groups showed some organ pathology, the heart tissue appeared edema and inflammation; lung tissue suffered inflammatory cell infiltration; the liver tissue appeared cell swelling, inflammation even necrosis of the dot changes; Kidney tissue performanced obvious edema, vasodilation, inflammation and even appeared protein casts and calcium deposition; and compared with separate disease groups, group H showed more obvious pathological changes.4. Immunohistochemical results showed that the TXNIP expression level of kidney in each experimental group rabbits was increased, and the TXNIP expression in group H was obviously higher than group Tp and group DM(P<0.05).Conclusion: 1.Injecting alloxan first,then vacciating T.pallidum can build a stable rabbit models of diabetes mellitus combined with syphilis.2. With the progression of disease, The diabetes mellitus combined with syphilis disease have more severe function and histopathological damage in liver and kidney than a single disease, meanwhile, the degree of tissue damage in heart and lung were increased significantly.3. Kidney injury mechanism of the diabetes mellitus combined with syphilis disease may relate to high expression of TXNIP.