| Summary: | 碩士 === 國立臺灣大學 === 解剖學暨細胞生物學研究所 === 100 === Introduction：Intestinal ischemia-reperfusion (IIR)injury is an important clinical problem occurring in, for example, mesenteric arterial obstruction and intestinal transplantation. IIR injury leads to systemic inflammatory response (SIRS), multiorgan dysfunction response and even mortality. In this study, we explored the protective effect and mechanism of ischemic postconditioning (IPoC), a modulation of reperfusion maneuver, on IIR injury in a rat models.
Materials and methods：Male Wistar rats weighing 200 ~300 g were used. IIR injury was induced by clamping superior mesenteric artery (SMA) for 30 minutes and de-clamping for 60 minutes (I/R group). Three cycles of 30 seconds of reperfusion followed by 30 seconds of ischemia was performed just before reperfusion began in IPoC group. Carboxy- atractyloside (CATR, a mitochondria permeability transition pore activator)was injected at 5 minutes before intestinal ischemia in IPoC+CATR group. NIM811 (a mitochondria permeability transition pore inhibitor)was injected 15 minutes after ischemia began in I/R+ NIM811 group. The blood samples and jejunum were collected at indicated time for analysis including serum levels of lactate dehydrogenase (LDH), the expression of small intestinal fatty acid binding protein (I-FABP)in portal blood , hematoxylin-Eosin staining and TUNEL assay of intestinal sections, the expressions of cytochrome c cleaved-of caspase 3 and malonialdehyde (MDA)in the small intestine mucosa.
Results： Compared to the sham group, serum LDH values, I-FABP expression, Chiu''s injury score, crypt/villus ratio (C/V ratio), the apoptotic index , expressions of cytochrome c, cleaved-caspase 3 and MDA are significantly higher than in the IR group (p<0.05) (LDH: 1273.67 277.43 U/L v.s. 3427±236.81 U/L , Chiu''s score: 0 v.s. 4, C/V ratio: 0.38±0.02 v.s. 0.72±0.12, apoptotic index: 0 v.s. 59.5±4.56 %, MDA: 5.43±0.27 v.s. 8.68±0.36). The IIR injury was lessened in the IPoC group and I/R+ NIM811 group , when compared with those of the I/R group(LDH: 1190.5±36.67 U/L & 1399.33±295.64 U/L, Chiu''s score: 0.2±0.2 & 0.4±0.24, C/V ratio: 0.39±0.03 & 0.37±0.02, apoptotic index: 15.7±15.7 % & 3.51±3.51 %, MDA: 5.58±0.27 & 6.45±0.13). On the other hand, the administration of CATR mitigated the protection offered by IPoC. (LDH: 2002±370.89 U/L, I-FABP: 182.09±70.43, Chiu''s score: 4.2±0.2, C/V ratio: 0.80±0.08, apoptotic index: 67.07±9.33 %, MDA: 10.03±0.23)
Conclusion：This study demonstrated ischemic postconditioning can reduce cell damage caused by intestinal ischemia and reperfusion injury, and the protective mechanism of IPoC was related with the modulation of mitochondrial permeability transition.
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