Takeuchi K, Ohuchi T, Harada H, Okabe S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Dig Dis Sci. 1995 Feb;40(2):274-81. doi: 10.1007/BF02065409.
The effects of urea-urease-ammonia on the rat gastric mucosa were examined and compared with those of NH4OH and NH4Cl. The mucosal application of urea with urease produced a reduction in potential difference (PD) in a dose-related manner for urea, and a significant drop was observed by > 0.1% urea in the presence of 100 units urease. Such PD reduction was also observed when the mucosa was exposed to either NH4OH (> 0.03%) or NH4Cl (> 1%); delta PD (20 mV) caused by 0.3% NH4OH and 3% NH4Cl was equivalent to that induced by 0.5% urea+urease (100 units). The combined oral administration of urea (approximately 6%) and urease (100 units) did not induce any macroscopic damage in the gastric mucosa. NH4Cl given orally had no or little effect on the mucosa at any dose levels even at 10%, while NH4OH given orally caused hemorrhagic lesions in the mucosa at the dose of > 0.3%. In contrast, both urea+urease and NH4Cl given prior to HCl/ethanol protected the gastric mucosa against damage in a dose-related manner, and a significant effect was obtained by urea at > 0.5% and by NH4Cl at > 1%. NH4OH was also effective in reducing the severity of HCl/ethanol-induced gastric lesions at lower dose (0.3%). The protective effect of urea+urease was attenuated significantly by prior administration of indomethacin or coadministration of hydroxyurea, while that of NH4Cl or NH4OH was mitigated by indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了尿素-脲酶-氨对大鼠胃黏膜的影响，并与氢氧化铵和氯化铵的影响进行了比较。将尿素与脲酶经黏膜给药，可使电位差（PD）以与尿素剂量相关的方式降低，在存在100单位脲酶的情况下，当尿素浓度>0.1%时，可观察到明显下降。当黏膜暴露于氢氧化铵（>0.03%）或氯化铵（>1%）时，也观察到这种PD降低；0.3%氢氧化铵和3%氯化铵引起的δPD（20 mV）相当于0.5%尿素+脲酶（100单位）引起的δPD。口服尿素（约6%）和脲酶（100单位）的联合给药未引起胃黏膜的任何宏观损伤。口服氯化铵在任何剂量水平（即使是10%）对黏膜都没有或几乎没有影响，而口服氢氧化铵在剂量>0.3%时会引起黏膜出血性病变。相比之下，在盐酸/乙醇之前给予尿素+脲酶和氯化铵均以剂量相关的方式保护胃黏膜免受损伤，当尿素>0.5%和氯化铵>1%时可获得显著效果。氢氧化铵在较低剂量（0.3%）时也能有效减轻盐酸/乙醇诱导的胃损伤的严重程度。预先给予吲哚美辛或同时给予羟基脲可显著减弱尿素+脲酶的保护作用，而吲哚美辛可减轻氯化铵或氢氧化铵的保护作用。（摘要截短至250字）
