Abstract: Objective To investigate the cardiorenal protective effects of renal sympathetic denervation(RSD) in rats with chronic kidney disease (CKD). Methods Rats were divided into five groups (n=6 per group): sham-operated group,5/6 nephrectomy-induced chronic kidney injury (CKI) model group, RSD group, metoprolol group, and perindopril group. Systolic blood pressure (SBP) and heart rate were measured noninvasively using the tail-cuff method at weeks 4 and 8. Cardiac ultrasonography was performed to assess left ventricular end-diastolic posterior wall thickness (PWTd), interventricular septal thickness at end-diastole (IVSTd),ejection fraction (LVEF), and left ventricular mass (LV mass). Blood and urine samples were collected for biochemical analysis. At week 8, heart and kidney tissues were collected for histopathological examination. Masson's trichrome staining was used to evaluate cardiac and renal fibrosis. Serum levels of IL-1β, IL-6, TNF-α, and TGF-β1 were measured by ELISA. Protein expression of Smad2/3, p-Smad2/3, α-SMA, Collagen1, and TGF-β1 in cardiac tissue was analyzed by Western blot. Results Compared with the sham group, the model group exhibited significantly elevated SBP, increased IVSTd, LVPWd, and LV mass, higher levels of urinary protein (UP), creatinine (Cr), blood urea nitrogen (BUN), uric acid (UA), and brain natriuretic peptide (BNP) and reduced LVEF as well as kidney volume (K Vol)(all P＜0.05). In contrast, all intervention groups (RSD, metoprolol, perindopril) exhibited significant reductions in SBP, IVSTd, LVPWd, LV mass, and lower levels of UP, Cr, BUN, UA, and BNP, as well as improved LVEF compared to the model group (P＜0.05). The model group had elevated serum level of all four inflammatory cytokines. In contrast, the RSD, metoprolol, and perindopril groups exhibited significant reductions in IL-6 and TGF-β1 compared to the model group (P＜0.05). Histopathological analysis revealed disorganized myocardial fibers with interstitial fibrosis in the model group, as well asglomerular atrophy, tubular degeneration/dilation, and marked interstitial fibrosis with inflammatory infiltration in renal tissue. All intervention groups (RSD, metoprolol, perindopril) showed attenuated fibrotic changes (P＜0.05). Tyrosine hydroxylase (TH) immunostaining showed greater sympathetic activation in the model group, which was ameliorated by all interventions (P＜0.05). Western blot analysis confirmed up-regulated cardiac expression of TGF-β1, p-Smad2/3, α-SMA, and Collagen Ⅰ(P＜0.05). These fibrotic markers were significantly downregulated in all treatment groups relative to the model group (P＜0.05), with perindopril showing the most pronounced effects. Conclusions Renal sympathetic denervation alleviates cardiorenal injury in CKD rats by mitigating fibrosis and suppressing IL-6/TGF-β1-mediated inflammation.

Key words: renal sympathetic denervation, chronic kidney disease rats, inflammatory factors, renal and myocardial fibrosis