Castell J V, Friedrich G, Kuhn C S, Poppe G E
Unidad de Hepatología Experimental, Hospital Universitario La Fe, Valencia, Spain.
Am J Physiol. 1997 Jul;273(1 Pt 1):G139-46. doi: 10.1152/ajpgi.1997.273.1.G139.
The human adult intestinal epithelium has traditionally been described as nonpermeable to proteins. However, indirect evidence suggests that reduced absorption of undegraded proteins might take place under physiological conditions. Using bromelain (an enzyme obtained from pineapple stems) as a model protein, we studied the extent of this mucosal permeation in 19 healthy men. The protein was detected in plasma by immunoassay and by its proteolytic activity after oral administration. The estimated plasma half-life was 6-9 h. After oral multidosing (3 g/day), plasma concentration reached as much as 5,000 pg/ml by 48 h. From the plasma concentration curve, it could be estimated that an average of 10.8 micrograms of bromelain was present in plasma in the 3- to 51-h period. The presence of undegraded bromelain in plasma was shown unequivocally by immunoprecipitation of plasma samples with antibromelain antibodies, followed by gel electrophoresis and immunodetection. Moreover, the enzyme retained its biological activity, at least in part. Circulating bromelain was found associated with alpha 2-macroglobulin and alpha 1-antichymotrypain. The results of this work confirm the existence of a small but significant intestinal transport of undegraded proteins in healthy men.
传统观点认为,人类成年肠道上皮对蛋白质是不可渗透的。然而,间接证据表明,在生理条件下可能会发生未降解蛋白质吸收减少的情况。我们以菠萝蛋白酶(一种从菠萝茎中提取的酶)作为模型蛋白,研究了19名健康男性中这种黏膜渗透的程度。口服给药后,通过免疫测定和蛋白水解活性在血浆中检测到该蛋白。估计血浆半衰期为6 - 9小时。口服多次给药(3克/天)后,48小时时血浆浓度高达5000皮克/毫升。从血浆浓度曲线可以估计,在3至51小时期间,血浆中平均存在10.8微克菠萝蛋白酶。通过用抗菠萝蛋白酶抗体对血浆样本进行免疫沉淀,随后进行凝胶电泳和免疫检测,明确显示血浆中存在未降解的菠萝蛋白酶。此外,该酶至少部分保留了其生物活性。发现循环中的菠萝蛋白酶与α2 - 巨球蛋白和α1 - 抗糜蛋白酶相关。这项工作的结果证实,在健康男性中存在少量但显著的未降解蛋白质的肠道转运。