Association of 72-kDa Heat Shock Protein Expression with Adaptation to Aspirin in Rat Gastric Mucosa
Association of 72-kDa Heat Shock Protein Expression with Adaptation to Aspirin in Rat Gastric Mucosa
复制标题
DOI：
10.1023/a:1026603919224
复制
发表时间：
1999-07
影响因子：
3.1
通讯作者：
M. Jin;M. Otaka;A. Okuyama;S. Itoh;S. Otani;M. Odashima;A. Iwabuchi;Noriaki Konishi;Isao Wada;I. Pacheco;H. Itoh;Y. Tashima;O. Masamune;Sumio Watanabe
中科院分区：
文献类型：
--
作者：
M. Jin;M. Otaka;A. Okuyama;S. Itoh;S. Otani;M. Odashima;A. Iwabuchi;Noriaki Konishi;Isao Wada;I. Pacheco;H. Itoh;Y. Tashima;O. Masamune;Sumio Watanabe
大量研究表明，在长期反复服用阿司匹林的情况下，胃粘膜可以增强其对阿司匹林引起的粘膜损伤的抵抗力。然而，这种适应的潜在机制还没有很好地建立。在本研究中，我们研究了长期（慢性）给药阿司匹林对大鼠胃粘膜中热休克蛋白（HSPs）表达的影响，热休克蛋白被称为内源性细胞保护剂。大鼠每天给予阿司匹林（100 mg/kg），持续20天。给药不同时间后，再给予大剂量阿司匹林（250 mg/kg），观察粘膜损伤情况。Western blot检测胃粘膜热休克蛋白（HSPs）的表达。用免疫组化方法研究各HSP在细胞内的定位。长期服用阿司匹林可引起胃粘膜对阿司匹林的抵抗，而HSP 60和HSP 90的表达无明显变化，HSP 72的表达增加与胃粘膜对阿司匹林的抵抗有关。免疫组化结果显示，HSP 72在粘膜表面细胞胞浆中表达增加。前列腺素E2水平受到抑制，而LTB 4水平无变化。结论：NSAIDs抑制胃粘膜PGE 2水平，提示HSP 72可能在胃粘膜适应中起重要作用。
It is well documented that gastric mucosa canincrease its resistance to mucosal damage caused byaspirin during repeated long-term administration ofaspirin. However, the underlying mechanism of thisadaptation is not well established. In the present study,we investigated the effect of long-term (chronic)administration of aspirin on expression of heat shockproteins (HSPs), which are known as endogenouscytoprotectants, in rat gastric mucosa. Rats were administeredaspirin (100 mg/kg) daily for up to 20 days. Aftervarious periods of aspirin administration, a high doseof aspirin (250 mg/kg) was administered, and the mucosal damage was assessed. Expression of heat shockproteins (HSPs) in gastric mucosa was evaluated byWestern blot. Intracellular localization of each HSP wasstudied immunohistochemically. ProstaglandinE2(PGE2) and leukotriene B4(LTB4) levels were also investigated.Long-term aspirin administration resulted in developmentof resistance to aspirin-induced mucosal damage, and theincrease of HSP72 expression correlated with mucosal resistance to aspirin.No significant increase was observed in HSP60 and HSP90levels. Immunohistochemical study showed an increase ofHSP72 in the cytoplasm of mucosal surface cells. The PGE2level was suppressed and nochange in the level of LTB4was observed. Itis possible that HSP72 could play important roles ingastric mucosal adaptation when the PGE2level is suppressed by NSAIDs.