Tetramethylpyrazine alleviates acute kidney injury by activating the Wnt/β-catenin pathway independent of DKK1.

Acute kidney injury (AKI) is a group of common clinical syndromes characterized by a rapid decline in renal function over a short period of time. At present, the treatment methods are limited, and research is needed to identify drugs that could alleviate renal ischemia-reperfusion (I/R) injury. Tetramethylpyrazine (TMP) is a bioactive alkaloid extracted from the Chinese herbal medicine Chuanxiong. TMP is known to possess various anti-inflammatory and cardiovascular and renal protective effects; however, the therapeutic molecular targets are still unclear. In the present study, using a rat renal I/R model, the effects of TMP on renal injury, dickkopf-1 (DKK1) expression, Wnt/β-catenin signaling and apoptosis were evaluated through morphological examination, renal function tests, western blotting, immunohistochemistry and TUNEL assays. It was determined that TMP ameliorated tubular pathologic injury and improved renal function in rats following renal I/R. In addition, in rats following I/R, TMP promoted the expression of DKK1, an inhibitor of the Wnt/β-catenin signaling pathway, in renal tissues, activated the Wnt/β-catenin signaling pathway in kidney tissues and reduced apoptosis of renal cells. To the best of our knowledge, the present study is the first to investigate the regulatory effects of TMP on DKK1 and the Wnt/β-catenin signaling pathway, revealing that TMP could attenuate AKI by activating Wnt/β-catenin signaling independent of the inhibitory effect of DKK1.