| dc.description.abstract | Background
Tuberculous spondylitis is a disease that occurs throughout the world. The
diagnosis can usually only be made at an advanced stage with severe spinal
deformity and significant neurological deficits such as paraplegia. Due to chronic
inflammation in bone, there will be an increase in cellular immune response and the
release of inflammatory cytokines, which will eventually trigger an increase in the
expression of matrix metalloproteinases (MMP). In vitro studies, doxycyline
inhibited MMP secretion induced by TB infection. This study assessed the effect of
doxycycline on MMP-9 expression in rabbits exposed to tuberculous spondylitis by
immunohistochemical examination.
Methods
This randomized controlled trial study was carried out from January to June 2020.
Adult New Zealand rabbits (Oryctolagus cuniculus) were used in this study. A total
of 40 rabbits were included in this study. The inoculation of Mycobacterium
tuberculosis procedure was carried out in groups. Doxycycline was administered to
the control group, the group with a dose of 1 mg/kgBW/day, and the group with a
dose of 5 mg/kgBW/day for each group based on time. . The outcome of this study
was the examination of the IHC expression of MMP-9 from blood samples after
doxycycline administration.
Result
Forty rabbits inoculated with Mycobacterium tuberculosis and treated with
doxycycline for 4 weeks were incubated in individual cages in one large room. The
rabbit's appetite does not decrease; the rabbits can defecate and urinate normally,
remain active, and respond to the environment well. Four rabbits died during the experiment. There was no significant differences in MMP-9 expression between the
control group and intervention group at 2 and 4 weeks. Meanwhile, MMP-9
expression was found greater at 6 and 8 weeks during doxycycline administration
between the control and intervention groups.
Discussion
MMP-9 regulates monocyte recruitment to granulomas in a zebrafish model,
suggesting that MMP modulates the immune response against Mycobacterium
tuberculosis (Mtb) and triggers pathological conditions. Many tetracyclines,
including DOX, have anti-inflammatory properties mediated by suppressing tumor
necrosis factor (TNF-α) and matrix metalloprotease (MMP). In vitro, DOX
inhibited MMP secretion induced by Mtb infection at 5 mg/liter and higher.
Doxycycline can inhibit MMP activity in cellular tuberculosis models, and the
decrease in MMP level was associated with reduced tissue damage in tuberculosis
infection. In this study, it was seen that at 6 and 8 weeks of inoculation, doxycycline
administration with MMP-9 had p-values of 0.023 and 0.038, respectively (p<0.05).
These results indicated a relationship between doxycycline administration and
MMP-9 based on immunohistochemistry at 6 and 8 weeks of inoculation. A positive
effect of doxycycline administration with MMP-9 based on immunohistochemistry
in rabbits inoculated for 6 and 8 weeks. This may be because the
immunohistochemical examination did not show any significant changes with
doxycycline administration for 6 and 8 weeks or the lack of samples. Several studies
showed that doxycycline can suppress the colony forming unit (CFU) of TB lung
and was positively correlated with the percentage of guinea pig granulomatous
infiltrates.
Conclusion
Based on the results of this study, there is a positive relationship and effect between
doxycycline administration and MMP-9 expression based on immunohistochemical
examination of rabbits inoculated for 6 and 8 weeks. | en_US |
