Matrix metalloproteinaze inchibitors system and experimental drug-resistant kidney tuberculosis treatment effectiveness

Abstract

BACKGROUND: Nephrotuberculosis is characterized by the accumulation of extracellular matrix proteins, the regulation of which is carried out by matrix metal propriets (MMP). AIM: To study the dynamics of the MMP / inhibitors of the blood in the treatment of experimental nephrotuberculosis using mesenchymal stem cells (MSC). MATERIALS AND METHODS: Among the 20 rabbits with nephrotuberculosis caused by the Mycobacterium tuberculosis, the group 1 compiled by untrue animals; group 2 — with anti-tuberculosis therapy; group 3 — with anti-tuberculosis therapy and mesenchymal stem cells. The development of nephrotuberculosis was confirmed by the reaction with Diaskintest. In the blood serum, the levels of MMP (MMP-1,-9), their tissue inhibitor-TIMP-1, cystatin C (CC), creatinine (KR), albumin (AL), ceruloplasmin (CP), neutrophilic elastasis (NE) and adenosin deaminase (ADA) were determined. A histological examination of the kidneys was carried out. Used Statistica 7.0. RESULTS: The presence of specific inflammation in the kidneys by 2.5 weeks in all groups was confirmed by increased levels of ADA, CP and a decrease in the body weight of animals, but was not accompanied by changes in the MMP-1,-9, TIMP-1, CC and KR. By the 21st week after infection in all groups, an increased level of ADA, NE and the KR was preserved, and the concentrations of CP and AL were normalized. In group 1 alone, high levels of MMP-9 and CC, foci of specific inflammation and distinct glomerulus changes were noted. The differences between the groups 3 and 2 were associated with lower values of the area of interstitial fibrosis and collagen (p = 0.03). A discriminant function based on the values of the MMP-1,-9, TIMP-1, NE, KR and CC, characterizing significant differences between three groups has been obtained. CONCLUSIONS: 1. Nephrotuberculosis in rabbits infected with the Mycobacterium tuberculosis 5582 Beijing genotype, after 2.5 weeks was characterized by an increase in the blood of ADA, NE, CP and a decrease in AL, and the lack of changes in the MMP-1,-9 and TIMP-1, KR and CC. 2. The processing of nephrotuberculosis was accompanied by an increase in the blood of concentrations of hell, NE and KR, MMP-9 and CC, but not MMP-1 and TIMP-1. 3. The therapy of the anti-tuberculosis and mesenchymal stem cells normalized the levels of the MMP-9 and the CC, but not ADA and NE. 4. The complex from MMP-1,-9, TIMP-1, NE, KR and CC, allows you to differentiate groups with different vephrotuberculosis activity.