高血尿酸对大鼠心肌组织核因子-kB表达线粒体锰超氧化物歧化酶活性的影响

The effect of hyperuricemia on nuclear factor-kB in myocardial tissue Mn superoxide dismutases activity in mitochondria of rats

目的研究高血尿酸对不同年龄组大鼠心肌组织NF-kB表达、线粒体锰超氧化物歧化酶（Mn—SOD）活性及心功能的影响。方法取SD雄性大鼠60只，其中青年组[2月龄，（200±20）g]30只，老年组[24月龄，（470±20）g]30只，2组中又分为对照组和高尿酸组，每组15只。用酵母膏联合乙胺丁醇灌胃法建立高尿酸大鼠模型；心导管插管测定左心室收缩压（LVSP），左心室舒张末压（LVEDP）及左心室压力上升和下降最大速度（±dp／dt max）。采用化学比色法检测心肌组织中Mn-SOD活性；免疫组织化学、反转录（RT）-PCR检测心肌组织中NF-kB基因和蛋白表达情况；统计分析采用单因素方差分析，多个样本均数比较采用SNK-q检验。结果高血尿酸对青年组和老年组大鼠心功能未造成明显影响，但对心肌组织中NF-kB的基因、蛋白表达和线粒体Mn-SOD活性造成影响，引起NF-kB基因、蛋白表达和Mn—SOD活性增高（F=85．4284、120．6830和398．2283，P〈0．01），且青年高尿酸组大鼠NF-kB基因、蛋白表达和Mn—SOD活性增高幅度高于老年高尿酸组（q=6．8186，10．6936，18．8779，P〈0．05）。结论高血尿酸一方面可能引起心肌组织中炎症反应，氧自由基增加，但另一方面可能通过提高线粒体Mn—SOD活性，清除氧自由基能力增强，从而减轻心肌组织中的炎症反应，保护心功能维持正常水平；且青年组对血尿酸增高的反应强于老年组。

Objective To investigate the effect of hyperuricemia （HUA） on nuclear factor-kB （NF-kB） in myocardial tissue, Mn superoxide dismutases （Mn-SOD） activity in mitochondria, cardiac function of rats with HUA. Methods Sixty SD male rats, including 30 young rats and 30 aged rats, were randomly divided into four groups： the young control group, the young HUA group, the aged control group and the aged HUA group. Fifteen rats were in each group. The HUA rat models were set up by lavage method with yeast extract and ethambutol. Left ventricular systolic pressure （LVSP）, left ventricular end-diastolic pressure （LVEDP） and left ventricular pressure at the end of the rising and falling maximum velocity （＋dp/dt,,~ were determined by intubation in the left ventricle with cardiac catheter. Mn-SOD activity in the mitochondria of rat myocar- dial tissue was detected by chemical colorimetry. The expressions of NF-kB in rats myocardial tissue were measured by immunohistochemistry （IHC） and reverse transcription polymerase chain reaction （RT-PCR）. Differences between groups were analyzed with One way analysis of variance, Student-Newman-keuls q test was used to compare the mean of multiple samples. Results Hyperuricemia had no significant effect on the cardiac function of HUA groups （P〉0.05）. But the gene and protein expression of NF-kB in myocardial tissue and Mn-SOD activity of mitochondria were impacted by HUA. Both the gene and protein expression of NF-kB and the activity of Mn-SOD in HUA groups were increased （F=85.428 4, 120.683 0 and 398.228 3, P〈0.01）. Furthermore, the increase of gene and protein expression of NF-kB and the Mn-SOD activity in rats myocardial tissue of young HUA group were higher than those in aged HUA group （q=6.818 6, 10.693 6 and 18.877 9, P〈0.05）. Conclusion Hyperuricemia may cause inflammation and increase oxygen free radicals in myocardial tissue on one hand, and it may reduce inflammation and protect the myocardial tissue by increasing the activity of Mn-SOD in myocardial mitochondria of HUA rats, and removing the oxygen free radicals on the other hand. The response to uric acid in young HUA group is stronger than that in the aged HUA group.