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

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 21^st 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.