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Ischemia-reperfusion injury(IRI) is closely related to inflammatory response. It can protect the myocardium IRI by controlling of inflammatory response. Water-soluble chitosan(WSC) has an effect on anti-oxidation and anti-inflammatory response. There is little literature on whether WSC can control myocardial IRI. In this study, we investigate the protective effects of WSC on myocardial IRI in rats and its mechanism, to provide experimental basis for drug prevention and treatment of myocardial IRI.
60 SD rats were randomly divided into sham operation group, IRI model group, low dose WSC group, medium dose WSC group, high dose of WSC group, 12 rats in each group. Among them, the IRI model group and each dose group WSC rats by left thoracotomy anterior interventricular branch of left coronary artery was ligated to establish IRI rat model, the rats in the sham operation group only isolated without ligation of the left anterior descending coronary artery. Sham operation group and IRI model group were given normal saline 10 ml/kg, low dose WSC group, middle dose of WSC group and high WSC group were given 120 mg/kg, 180 mg/kg and 240 mg/kg, by gavage once a day, the rats were sacrificed after 15d, heart blood, serum separation, ELSIA was used to detect the serum IL-6 and TNF-α levels. Near the apex of 1/3 parallel to the atrioventricular groove of transverse cut fresh myocardial tissue after fixation, paraffin embedding. The morphological changes of myocardial tissue were observed with HE staining. The expression of UCP2 mRNA in detecting myocardial tissue was observed with RT-PCR.
1.Under the light microscope, in sham operation group, the myocardial fibers arranged orderly, clear structure, clear nuclear staining, and myocardial interstitial has no inflammatory cell infiltration. In IRI model group rats myocardial fibers showed disorder, boundary was not clear, and lightly stained cytoplasm, nucleus condensed or dissolved, a large number of inflammatory cells infiltration, hyperemia, congestion, myocardial fiber stripes disappear, myocardial tissue necrosis were observed. In intervention group WSC showed muscle fiber melt fracture phenomenon of myocardial cells, granular degeneration,edema,inflammatory cell infiltration and occasional.
2.The myocardial tissue level of IL-6,TNF-α in IRI model group were significantly increased than the sham operation group(76.12±4.93pg/ml, 56.43±8.24pg/ml, vs 51.00±3.58pg/ml, 30.59±6.51pg/ml, P<0.01). 3.The myocardial tissue level of IL-6, TNF-α in low, medium and high dose of WSC group were significantly reduced than the IRI model group(IL-6: 72.67±7.93pg/ml, 64.39±7.16pg/ml, 57.71±3.34pg/ml vs 76.12±4.93pg/ml; TNF-α: 49.28±7.13pg/ml, 43.01±5.14pg/ml, 37.05±6.21pg/ml vs 56.43±8.24pg/ml; P<0.05, P<0.01).4.The UCP2 mRNA expression in IRI model group were significantly increased than the sham operation group, while significantly reduced in each dose of WSC group(P<0.05, P<0.01).
Inflammation is involved in myocardial IRI. WSC protect the myocardial IRI by controlling of the inflammatory response.