The role of mitochondrial permeability transition pore in ischemic post-conditioning for counteracting small intestinal ischemia-reperfusion injury in rabbits
Jianxin Dong, Mu Yang, Juwen Zhang, Lubin Li, Haijie Che, Jun Yong, Song Fubo
Abstract
Jianxin Dong, Mu Yang, Juwen Zhang, Lubin Li, Haijie Che, Jun Yong, Song Fubo
Abstract
Objective To investigate the role of mitochondrial permeability transition pore (mPTP)in ischemic post-conditioning for counteracting small intestinal ischemia-reperfusion(I/ R)injury in rabbits. Methods Forty New Zealand rabbits were randomly divided into sham-operated group(Sham group), I/R group,ischemic post-conditioning group(IPO group), mPTP inhibitor cyclosporine A group(Cs A group), and IPO+ mPTP agonist atraotydin group(IPO+ Atr group).Parts of small intestine tissues were collected from each group of rabbits after intervention for hematoxylin-eosin(HE) staining. Malondialdehyde(MDA) activity in small intestine tissue was measured by the relevant kit.The mitochondria were isolated and mPTP opening was detected by relevant kits.Intestinal mucosal injury was observed by Chiu's grade 6 scoring method.The apoptosis of intestinal epithelial cells was examined by Td T-mediated d UTP nick end labeling(TUNEL) assay. Results As compared with Sham group, mPTP opening in I/R group was significantly increased(3. 53±0. 36 vs. 1. 37±0. 16, P< 0. 05); MDA activity was significantly increased[(0. 98±0. 14) nmol/mg vs. (0. 34±0. 03) nmol/mg, P< 0. 05]; intestinal mucosa score was significantly increased(4. 66± 0. 41 vs.0. 92±0. 58, P< 0. 05); apoptosis index of intestinal cells was significantly increased [(60. 34±6. 02)% vs.(4. 65±1. 68)%, P< 0. 05].As compared with I/R group, mPTP openings in IPO group and Cs A group were significantly decreased(2. 32±0. 23 and 2. 62±0. 18 vs.3. 53± 0. 36, P< 0. 05); MDA activity was significantly decreased[(0. 55±0. 04) and(0. 62±0. 06) nmol/mg vs.(0. 98±0. 14) nmol/mg, P< 0. 05]; intestinal mucosa score was significantly decreased(3. 25±0. 27 and 3. 52±0. 55 vs.4. 66±0. 41, P< 0. 05); apoptosis of intestinal cells was significantly decreased[(28. 33±3. 20)% and(20. 49±4. 10)% vs.(60. 34±6. 02)%, P< 0. 05]. As compared with IPO group, mPTP openings in IPo+ Atr group were significantly increased(2. 32 ±0. 23 vs.1. 05±0. 16, P< 0. 05); MDA activity was significantly increased[(1. 08±0. 18) vs. (0. 55±0. 04) nmol/mg, P< 0. 05]; intestinal mucosa score was significantly increased(4. 57± 0. 32 vs.3. 25±0. 27, P< 0. 05); apoptosis index of intestinal cells was significantly increased [(40. 35±2. 18)% vs.(28. 33±3. 20)%,P< 0. 05]. Conclusion The mechanism of ischemic post-conditioning for counteracting intestinal ischemia-reperfusion injury in rabbits may be associated with the inhibition of mitochondrial permeability transition pore opening. Key words: Mitochondrial permeability transition pore; Ischemic post-conditioning; Intestine ischemia; Reperfusion injury
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Objective To investigate the role of mitochondrial permeability transition pore (mPTP)in ischemic post-conditioning for counteracting small intestinal ischemia-reperfusion(I/ R)injury in rabbits. Methods Forty New Zealand rabbits were randomly divided into sham-operated group(Sham group), I/R group,ischemic post-conditioning group(IPO group), mPTP inhibitor cyclosporine A group(Cs A group), and IPO+ mPTP agonist atraotydin group(IPO+ Atr group).Parts of small intestine tissues were collected from each group of rabbits after intervention for hematoxylin-eosin(HE) staining. Malondialdehyde(MDA) activity in small intestine tissue was measured by the relevant kit.The mitochondria were isolated and mPTP opening was detected by relevant kits.Intestinal mucosal injury was observed by Chiu's grade 6 scoring method.The apoptosis of intestinal epithelial cells was examined by Td T-mediated d UTP nick end labeling(TUNEL) assay. Results As compared with Sham group, mPTP opening in I/R group was significantly increased(3. 53±0. 36 vs. 1. 37±0. 16, P< 0. 05); MDA activity was significantly increased[(0. 98±0. 14) nmol/mg vs. (0. 34±0. 03) nmol/mg, P< 0. 05]; intestinal mucosa score was significantly increased(4. 66± 0. 41 vs.0. 92±0. 58, P< 0. 05); apoptosis index of intestinal cells was significantly increased [(60. 34±6. 02)% vs.(4. 65±1. 68)%, P< 0. 05].As compared with I/R group, mPTP openings in IPO group and Cs A group were significantly decreased(2. 32±0. 23 and 2. 62±0. 18 vs.3. 53± 0. 36, P< 0. 05); MDA activity was significantly decreased[(0. 55±0. 04) and(0. 62±0. 06) nmol/mg vs.(0. 98±0. 14) nmol/mg, P< 0. 05]; intestinal mucosa score was significantly decreased(3. 25±0. 27 and 3. 52±0. 55 vs.4. 66±0. 41, P< 0. 05); apoptosis of intestinal cells was significantly decreased[(28. 33±3. 20)% and(20. 49±4. 10)% vs.(60. 34±6. 02)%, P< 0. 05]. As compared with IPO group, mPTP openings in IPo+ Atr group were significantly increased(2. 32 ±0. 23 vs.1. 05±0. 16, P< 0. 05); MDA activity was significantly increased[(1. 08±0. 18) vs. (0. 55±0. 04) nmol/mg, P< 0. 05]; intestinal mucosa score was significantly increased(4. 57± 0. 32 vs.3. 25±0. 27, P< 0. 05); apoptosis index of intestinal cells was significantly increased [(40. 35±2. 18)% vs.(28. 33±3. 20)%,P< 0. 05]. Conclusion The mechanism of ischemic post-conditioning for counteracting intestinal ischemia-reperfusion injury in rabbits may be associated with the inhibition of mitochondrial permeability transition pore opening. Key words: Mitochondrial permeability transition pore; Ischemic post-conditioning; Intestine ischemia; Reperfusion injury
Key concepts: MPTP, Mitochondrial permeability transition pore, TUNEL assay, Apoptosis, Ischemia, Reperfusion injury, Malondialdehyde, Small intestine