Schwarzenberg S J, Sharp H L, Manthei R D, Seelig S
Hepatology. 1986 Nov-Dec;6(6):1252-8. doi: 10.1002/hep.1840060605.
We quantitated alpha 1-antitrypsin mRNA in normal, alpha 1-antitrypsin-deficient cirrhotic and biliary cirrhotic livers using two-dimensional electrophoretograms of [35S]methionine-labeled translational products of total hepatic RNA and RNA/DNA hybridization. alpha 1-Antitrypsin precursor product was identified by immunoprecipitation. The relative abundance of alpha 1-antitrypsin product from normal (0.989 +/- 0.197), cirrhotic (0.956 +/- 0.062) and alpha 1-antitrypsin deficient (0.818 +/- 0.12) livers was not significantly different. Although (RNA/DNA) was decreased in the PiZZ cirrhotic livers compared to normal (0.56 +/- 0.045 vs. 0.95 +/- 0.225), it equaled that found in the PiM cirrhotic livers (0.56 +/- 0.055). The concentration of alpha 1-antitrypsin mRNA [relative abundance X (RNA/DNA)], while decreased in PiZZ compared to normal liver, is thus no different in PiZZ cirrhotics than in PiM cirrhotics. We confirmed this observation by quantitation of the alpha 1-antitrypsin mRNA using an alpha 1-antitrypsin genomic probe. By RNA/DNA hybridization, alpha 1-antitrypsin mRNA was equal in PiM cirrhotic and PiZZ cirrhotic (38.48 +/- 4.5 vs. 31.93 +/- 2.1), but significantly decreased from noncirrhotic PiM liver (58.36 +/- 12.7). We conclude that alpha 1-antitrypsin mRNA is decreased in cirrhosis of any etiology, and this decrease appears to represent a general response of the liver to injury. Since the decreased alpha 1-antitrypsin mRNA in PiM cirrhotics is associated with normal serum alpha 1-antitrypsin levels, it is unlikely that the decreased alpha 1-antitrypsin mRNA in PiZZ cirrhotics accounts for their decreased serum levels.
我们使用总肝RNA和RNA/DNA杂交的[35S]甲硫氨酸标记翻译产物的二维电泳图谱，对正常、α1-抗胰蛋白酶缺乏性肝硬化和胆汁性肝硬化肝脏中的α1-抗胰蛋白酶mRNA进行定量。通过免疫沉淀鉴定α1-抗胰蛋白酶前体产物。来自正常肝脏（0.989±0.197）、肝硬化肝脏（0.956±0.062）和α1-抗胰蛋白酶缺乏肝脏（0.818±0.12）的α1-抗胰蛋白酶产物的相对丰度无显著差异。尽管与正常肝脏相比，PiZZ肝硬化肝脏中的（RNA/DNA）降低（0.56±0.045对0.95±0.225），但与PiM肝硬化肝脏中的（RNA/DNA）相当（0.56±0.055）。因此，与正常肝脏相比，PiZZ肝硬化肝脏中α1-抗胰蛋白酶mRNA的浓度[相对丰度×（RNA/DNA）]降低，但PiZZ肝硬化患者与PiM肝硬化患者并无差异。我们使用α1-抗胰蛋白酶基因组探针定量α1-抗胰蛋白酶mRNA，证实了这一观察结果。通过RNA/DNA杂交，PiM肝硬化和PiZZ肝硬化中的α1-抗胰蛋白酶mRNA相等（38.48±4.5对31.93±2.1），但与非肝硬化PiM肝脏相比显著降低（58.36±12.7）。我们得出结论，任何病因的肝硬化中α1-抗胰蛋白酶mRNA均降低，这种降低似乎代表肝脏对损伤的一般反应。由于PiM肝硬化患者中α1-抗胰蛋白酶mRNA降低与血清α1-抗胰蛋白酶水平正常相关，因此PiZZ肝硬化患者中α1-抗胰蛋白酶mRNA降低不太可能是其血清水平降低的原因。
