To investigate the protective effect of pancreatic kininogenase (PK) on tacrolimus (TAC)-induced kidney injury in rats.

48 adult male Sprague-Dawley rats were randomly divided into four groups (12/group): (1) vehicle (VH) group: intraperitoneal injection of olive oil 1 ml/(kg·d) and normal saline 2 ml/(kg·d); (2) VH + PK group: intraperitoneal injection of olive oil 1 ml/(kg·d) and PK 7.2 U/(kg·d); (3) TAC group: intraperitoneal injection of TAC 1.5 mg/(kg·d) and normal saline 2 ml/(kg·d); (4) TAC + PK group: intraperitoneal injection of TAC 1.5 mg/(kg·d) and PK 7.2 U/(kg·d). After 4 weeks of the above treatment, the rats were sacrificed, and samples of blood, urine, and kidney tissues were collected. The general biochemical indicators and renal function were detected, and pathological observation was used to evaluate renal interstitial fibrosis. ELISA and Western blotting were used to detect the expression of inflammatory factors, fibrogenic factors, and antioxidants, and ELISA was also used to detect oxidative DNA markers.

Compared with the VH group, the TAC group had higher levels of serum creatinine (Scr) and blood urea nitrogen (BUN), more renal interstitial fibrosis, more expression of transforming growth factor-β1 (TGF-β1) and interleukin 6 (IL-6), higher levels of serum and urine 8-hydroxydeoxyguanosine (8-OHdG), and more expression of ectodermal dysplasia-1 (ED-1) and osteopontin (OPN) in cells (P<0.05), but showed lower level of manganese superoxide dismutase (MnSOD) (P<0.05). Compared with the TAC group, the TAC+ PK group had lower levels of Scr and BUN, less renal interstitial fibrosis, less expression of TGF-β1 and IL-6, lower levels of serum and urine 8-OHdG, and less expression of ED-1 and OPN in cells (P<0.05), but showed higher level of MnSOD (P<0.05).

PK treatment alleviated the TAC-induced renal insufficiency, renal interstitial fibrosis, interstitial inflammation, and oxidative stress. PK treatment may have a protective effect on TAC-induced kidney damage.