Peran Doksisiklin Sebagai MMP-1 Inhibitor pada Infeksi Spondilitis Tuberkulosis Model Kelinci

Abstract

Introduction It is estimated that approximately one third of the world's population is infected with the bacterium Mycobacterium tuberculosis, which is the cause of tuberculosis (TB) infection, although only 5% of those infected have clinical TB disease. Globally, it is estimated that approximately 10.0 million people (range, 9.0-11.1 million) will develop TB in 2017 with 5.8 million men, 3.2 million women and 1.0 million children. Pro-inflammatory and antiinflammatory cytokines play an important role in the development and control of Mycobacterium tuberculosis infection. Several cytokines have been known to be biomarkers of the activity of tuberculosis infection. Matrix metalloproteinase (MMP) is a zinc-dependent protease, which plays a role in extracellular matrix processing and modulates the inflammatory response by facilitating and inhibiting different cytokines. Several types of animals have been used to model tuberculosis, including rats, guinea pigs, rabbits, and primates. Until now it has not been reported that doxycycline as an MMP inhibitor will reduce the level of tissue damage in an animal model of tuberculous spondylitis which is characterized by a decrease in MMP-1 levels in serum and in vertebral body tissue. Method This research is an experimental study on rabbits with a randomized pre post control experimental study design. This research was conducted in February 2020 - May 2020. This study was divided into two stages, where the first stage of the first stage study used a total of 60 rabbits which were divided into four large groups. , with each group consisting of 15 rabbits. From 15 rabbits in each large group, 2 rabbits were used as control (without Mycobacterium tuberculosis inoculation). while the rest (13 tails) were to continue to the second stage of research. Then, M. tuberculosis was inoculated and an assessment was carried out. Incubation of M. tuberculosis was carried out for 2, 4, 6, and 8 weeks. The inoculation success rate was 37.5%. In the second stage of treatment. Rabbits that had been inoculated with M. tuberculosis were given doxycycline for 4 weeks. After that, doxycycline was given at a dose of 1 mg/kgBW/day and 5 mg/kgBW/day. The main outcomes were BTA staining, PCR, culture, histopathology, and MMP-1 immunohistochemistry. Results Administration of doxycycline give significant results (P <0.5) in the group with incubation of M. tuberculosis bacteria for 6 weeks with 5 mg/kgBW/day and incubation for 8 weeks with 1 mg/kgBW/day for doxycycline which is marked by decreased level of serum MMP-1. Conclusion Doxycycline can be used as one of the widely available MMP-1 inhibitor options, reducing MMP-1 expression and also suppressing the growth of tuberculosis mycobacteria. Further research is needed to determine the level of MMP-1 persists in the body and identify factors that scan cause MMP-1 levels to change.