title: [Protection of penehyclidine hydrochloride on renal tissue injury induced by limb ischemia/reperfusion].
abstract: OBJECTIVE
  To evaluate the protection of penehyclidine hydrochloric postconditioning on HIF-1α (hypoxia-inducible factor-1α) in renal tissue injury induced by lower limb ischemia/reperfusion (I/R).
  
  
  METHODS
  A total of 72 adult male Wistar rats weighing 230 - 250 g were randomly divided into 3 groups: control (group C), limb ischemia-reperfusion (group R/I) and penehyclidine hydrochloride postconditioning (group P). The animals were anesthetized by inhaling 2% isoflurane and blood flow of bilateral lower limbs was blocked with rubber bands for 3 h in groups P and R/I. In group P, penehyclidine hydrochloride 0.15 mg/kg was injected via caudal vein at 3 min pre-reperfusion. After sacrificing, their kidneys were removed at 3 h of ischemia and 1, 3, 6 h of reperfusion respectively. The blood urea nitrogen (BUN) and creatinine (Cr) were detected by colorimetric method, plasma tumor necrosis factor-α (TNF-α) by ELISA (enzyme-linked immunosorbent assay) and HIF-1α of renal tissue by immunohistochemistry. Renal pathological changes were observed under light microscope.
  
  
  RESULTS
  Compared with group C, the serum levels of BUN and Cr increased while TNF-α and HIF-1α were up-regulated in groups I/R and P (P < 0.05). As compared with group I/R, the serum levels of BUN, Cr and MDA decreased while TNF-α and HIF-1α were down-regulated in group P. [at T2: (15.10 ± 1.88) mmol/L vs (19.46 ± 2.76) mmol/L, (113 ± 10) µmol/L vs (143 ± 11) µmol/L, (13.8 ± 1.7) nmol/g vs (15.5 ± 1.8) nmol/g, (53.1 ± 3.1) ng/L vs (53.9 ± 4.8) ng/L, 0.298 ± 0.015 vs 0.471 ± 0.032, all P < 0.05].
  
  
  CONCLUSIONS
  Penehyclidine hydrochloride can down-regulate the expression of HIF-1α and attenuate the renal injury induced by lower limb I/R. And the mechanisms may be through inhibiting the inflammatory reactions, reducing the release of oxygen free radicals and improving the conditions of hypoxia and ischemia.
authors.affiliation: Department of Anesthesiology, Lanzhou University, Lanzhou, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Xue
authors.forename: Yu-fang
authors.initials: YF
authors.lastname: Leng
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Yu-qing
authors.initials: YQ
authors.lastname: Kang
mesh_terms: D000818:Animals; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011812:Quinuclidines; D017382:Reactive Oxygen Species; C486140:penehyclidine