高脂饮食对糖尿病大鼠心肌损伤的研究

目的 观察高脂饮食对糖尿病大鼠心肌炎症反应及纤维化的影响.方法 SD大鼠分为对照组（N组）、糖尿病组（D组）和高脂饮食组（H组）,每组20只,后两组用小剂量链脲佐菌素制备糖尿病大鼠模型.H组以高脂饲料喂养,其余两组以普通饲料喂养.12周后测血糖、血脂水平及左室质量指数（LVMI）,光镜下观察心肌结构,免疫组化法检测NF-κB、TNF-α表达,Western blot检测心肌组织基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）、金属蛋白酶组织抑制物-1（TIMP-1）表达情况.结果 光镜下可见N组大鼠心肌细胞排列整齐、致密,结构清晰.D组及H组大鼠心肌细胞排列紊乱、扭曲,间质有炎症细胞聚集.D组大鼠心肌NF-κB、TNF-α表达较对照组明显升高,H组心肌NF-κB、TNF-α表达明显较N组及D组升高,组间比较差异有统计学意义（P〈0.05）.D组及H组心肌MMP-2表达减低,MMP-9、TIMP-I表达均增加,但MMP-9/TIMP-1的比值下降,各组间比较差异有统计学意义（P〈0.05）.结论 糖尿病大鼠心肌损伤表现为心肌炎症反应和间质纤维化,高脂饮食通过上调NF-κB、TNF-α表达及影响MMP-2、MMP-9及TIMP-1的调节失衡对心肌造成损伤.

Effects of high-fat diet on myocardial injury in diabetic rats

Objective To investigate the effects of high-fat diet on myocardial inflammation and fibrosis of diabetic rats. Methods SD rats were randomly divided into 3 groups：the control group（N group）, the DM group（ D group）and the high-fat diet group（ H group）. The D group and the H group rats with diabetes by intrapefitoneal injection of low doses of streptosotocin. In N group and D group the rats were fed with normal food, in H group diabetes were fed with high-fat diet. After 12 weeks ,left ventricu- lar mass index（LVMI） was measured . The pathological changes in myocardial cells were observed under light microscope. The pro- teins of NF-κB and TNF-ct were assayed by immunohistoehemieal method . The expressions of MMP-2,MMP-9 and TIMP-1 were measured by Western blotting. Results It was showed that cardiac myocytes were compact and orderly with clear structure in N group. The cardiac myocytes were disorderly, distorted , with infiltration of inflammatory cells in the interstitium in D and H groups. The expression of NF-κB and TNF-α in D group increased significantly in the myocardium （ P 〈 0.05）. Compared with D group and N group, high-fat diet induced the expression of NF-κB and TNF-α （ P 〈 0.05 ）. The expressions of MMP-2 was reduced and MMP-9,TIMP-1 induced,but the ratio of MMP-9/TIMP-1 was decreased in D group and H group. Conclusion High-fat diet in- creased the expression of NF-κB and TNF-α and decreased the expression of MMP-2 in diabetic rats. These data suggesting that high-fat diet might play an important role in diabetic cardiomyopathy.