Changes of cholinergic nerves and tumor necrosis factor-α in doxorubicin-induced rat failing heart / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the changes of cholinergic nerves in doxorubicin (DOX)-induced rat failing heart and tumor necrosis factor-α (TNF-α) in the heart tissue and serum.</p><p><b>METHODS</b>Adult Sprague-Dawley rats were randomized into control (n=10) and DOX-induced chronic heart failure (CHF) groups (n=15), and in the latter group, the rats were given intraperitoneal injections of 2.5 mg/kg DOX once a week for 6 weeks, with a total cumulative dose of 15 mg/kg. The control rats were injected with normal saline (1 ml/week). Karnovsky-Roots histochemical staining combined with point counting was used to demonstrate the distribution of cholinergic nerves in the heart. The expression levels of TNF-α in the heart tissue and serum were determined with ELISA.</p><p><b>RESULTS</b>Positively stained cholinergic nerves were found in all the rat hearts in the two groups, but in CHF group, the point counts of cholinergic nerves were significantly lower than that of the control group (P<0.01). Compared with the control rats, those with DOX-induced CHF showed elevated levels of TNF-α both in the heart tissue and in the serum (P<0.01).</p><p><b>CONCLUSION</b>In rats with DOX-induced CHF, the parasympathetic nervous system is down-regulated in the failing heart, and the diminished cholinergic anti-inflammatory pathway may play an important role in the progression of CHF.</p>