重组人胰岛素样生长因子-I对心肌梗死大鼠心肌基质金属蛋白酶表达及心肌间质降解的影响

目的：探讨重组人胰岛素样生长因子-I（rhIGF-I）对心肌梗死（MI）大鼠心肌基质金属蛋白酶（MMPs）的表达及心肌间质降解的影响。方法：48只SD大鼠腹腔注射异丙基肾上腺素建立MI模型后随机分成3组，每组16只，术后分别给予rhIGF-I50μg·kg^-1·d^-1（IGF-I组）、奥曲肽50μg·kg^-1d·^-1d（Oct组）和生理盐水5mL·kg^-1d·d^-1d（MI组），每组按照用药时间（2、14d）再分成2个亚组（分别是IGF-I2d、IGF-I14d，Oct2d、Oct14d，和MI2d、MI14d组，N=8），另取8只正常SD大鼠作为阴性对照组。超声测定大鼠左室前壁（LVAW）、后壁（LVPW）厚度、左室收缩末期内径（LVESD）、左室舒张末内径（LVEDD）以及短轴缩短率（FS）；大鼠处死后消化法测定心肌组织匀浆羟脯氨酸浓度；免疫组织化学法检测基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）及基质金属蛋白酶组织抑制因子-1（TIMP-1）在心肌中的表达。结果：与MI组相比，IGF-I组大鼠梗死区心肌MMP-2、MMP-9活性降低，TIMP-1表达增加，心肌胶原降解减少，LVEDD、LVESD减小，FS增加；Oct组MMP-2、MMP-9表达增加，胶原蛋白降解显著，LVAW降低，LVEDD、LVESD增加，FS下降。结论：rhIGF-I治疗使MI大鼠心肌MMPs活性减弱，TIMP-1表达上调，心肌间质胶原降解减少，心室重构减轻。

Effects of recombinant human insulin-like growth factor-I on the ex- pression of matrix metalloproteinases and interstitial degradation of myocardial infarction rats

AIM. To examine the effect of re- combinant human insulin-like growth factor-I （rhIGF-I） on the expression of matrix metallo- proteinases （MMPs） and interstitial degradation of myocardium in postinfarction rats. METH- ODS： Seven-week old male Sprague-Dawley （SD） rats were intraperitoneally injected with i- soprenaline to establish myocardial infarction （MI） model. Forty-eight rats showed clear ECG evidence of infarction and were assigned random- ly to IGF-I group （rhIGF-I 50 μg · kg^-1 · d^-1 , i.v. ）, Oct group （ Octreotide 50μg. kg^-1· d ^-1, i.v.） or MI group （normal sodium 5 mL. kg^-1 · d^-1, i.v.）. Each group was divided into two subgroups （n=8, respec- tively） according to the treatment days, 2 or 14 days when the rats were sacrificed. Another 8 normal SD rats were selected as the control group. Transthoracic echocardiograms were per- formed to examine the thickness of anterior wall （LVAW） and posterior wall （LVPW） of left ventricle, left ventricular end-systolic diameter （LVESD）, left ventricular end-diastolic diame- ter （LVEDD）, and fractional shortening （FS） as well. The levels of MMP-2, MMP-9, TIMP-1 in myocardium were quantified with immunohisto-chemistry. Tissue homogenate myocardium hydroxyproline concentration was determined by pepsis method. RESULTS.Compared with the MI group, the expressions of MMP-2 and MMP-9 in rhIGF-I group were decreased, and the expres- sion of TIMP-1 in the infarcted areas was in- creased ; the degradation of myocardium collagen were decreased and the LVEDD and LVESD were decreased, the FS was increased; the ex- pressions of MMP-2 and MMP-9 in Oct group were increased, the degradation of myoeardium collagen was aggravated, the LVAW was de- creased, the LVEDD, LVESD were increased, the FS was decreased. CONCLUSION： rhIGF-I administered to rats after MI is associated with decreased activities of MMPs, substantial in- crease of expression of TIMP-1, and leads to at- tenuate interstitial degradation of myocardium and