[Protection of penehyclidine hydrochloride on renal tissue injury induced by limb ischemia/reperfusion].

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).
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.
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].
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.
AuthorsXing Xue, Yu-fang Leng, Yue Zhang, Yan Zhang, Tao Wang, Yu-qing Kang
JournalZhonghua yi xue za zhi (Zhonghua Yi Xue Za Zhi) Vol. 91 Issue 26 Pg. 1866-9 (Jul 12 2011) ISSN: 0376-2491 [Print] China
PMID22093793 (Publication Type: English Abstract, Journal Article)
Chemical References
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Quinuclidines
  • Reactive Oxygen Species
  • penehyclidine
  • Animals
  • Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
  • Kidney (drug effects, pathology)
  • Male
  • Quinuclidines (pharmacology)
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species (metabolism)
  • Reperfusion Injury (metabolism, pathology)

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