血清非对称性二甲基精氨酸在非酒精性脂肪性肝病大鼠模型肝脏炎症活动进程中的变化

Changes in serum asymmetric dimethylarginine levels in progression of liver inflammation in an experimental rat model of nonalcoholic fatty liver disease

目的利用非酒精性脂肪性肝病(NAFLD)大鼠模型观察血清非对称性二甲基精氨酸(ADMA)在NAFLD炎症进程的变化。方法肝组织标本及血清标本分别来自实验组高脂乳剂灌胃法成功构建的NAFLD模型(M组)及同期生理盐水灌胃替代构建的正常对照组(C组)。分别检测M组4、8、12周(M4、M8、M12)和C组12周(C12)大鼠血清ALT、ADMA水平及肝组织匀浆一氧化氮(NO)水平,同期评估各组肝脂肪炎症进程积分(NAS)。数据服从正态分布且方差齐,多组间比较应用单因素方差分析,进一步两两比较应用LSD-t法;服从正态分布且方差不齐,多组间比较应用Kruskal-Wallis H检验;相关性分析应用Pearson相关法。结果与C12组相比,M12组大鼠血清ALT、ADMA水平及肝组织匀浆NO水平显著升高,差异有统计学意义(P值分别为0.010、<0.001、<0.001)。血清ADMA与ALT水平无明显相关性(r=0.195,P=0.228),与肝组织匀浆NO水平、大鼠NAS呈正相关(r=0.631,P<0.001;r=0.782,P<0.001)。结论 NAFLD大鼠血清ADMA水平随肝组织脂肪炎症活动进程的加重而逐渐升高,且与肝组织炎症损伤因子NO水平、NAS呈正相关。ADMA作为一种新的炎症因子用于评估NAFLD肝组织慢性炎症程度值得进一步研究证实。

Objective To investigate the changes in serum asymmetric dimethylarginine （ADMA） levels in the progression of liver inflammation in a rat model of nonalcoholic fatty liver disease （NAFLD）. Methods The rat model of NAFLD was established through high - fat cream by gavage and these rats were considered the experimental group （group M）, and the rats in the normal control group （group C） were given normal saline by gavage within the same period of time. Liver samples and serum samples were collected from these rats. Serum alanine aminotransferase （ALT） and ADMA levels and the content of nitric oxide （NO） in liver tissue homogenate were measured at 4, 8, and 12 weeks for group M （M4, Ms, and M12 ） and 12 weeks for group C （C12）, and NAFLD activity score （NAS） was evaluated for both groups at the same time point. As for the data that were normally distributed and had homogeneity of variance, one - way analysis of variance was applied for comparison between multiple groups, and the least significant difference （LSD） t - test was applied for comparison within the same group; as for the data that were normally distributed and had heterogeneity of variance, Kruskal - Wallis H test was applied for comparison between multiple groups. Pearson correlation analysis was applied for correlation analysis. Results Compared with the C12 group, the MI2 group had significantly increased serum ADMA and ALT levels and content of NO in liver tissue homogenate （P = 0. 010, P 〈 0. 001, and P 〈 0.001, respectively）. Serum ADMA level was not significantly correlated with serum ALT level （ r = 0. 195, P = 0. 228 ） , and was positively correlated with the content of NO in liver tissue homogenate and NAS in rats （ r = 0. 631, P 〈 0. 001 ; r = 0. 782, P 〈 0. 001 ）. Conclusion In rats with NAFLD, serum ADMA level gradually increases with the progression of liver inflammation, and is positively corre- lated with the content of NO and NAS. The role of ADMA as a new inflammatory factor for evaluating the grade of chronic liver inflammation in NAFLD needs to be further investigated.