Cui L, Takagi Y, Wasa M, Sando K, Khan J, Okada A
Department of Pediatric Surgery, Osaka University Medical School, Suita, Osaka 565, Japan.
J Nutr. 1999 Apr;129(4):792-8. doi: 10.1093/jn/129.4.792.
A nitric oxide synthase (NOS) inhibitor, NG-nitro-L -arginine methyl ester (L-NAME), was given to zinc-deficient (ZD) rats to determine whether it prevents the intestinal damage usually observed under these conditions. Weanling male rats were given free access to a ZD diet (2 mg zinc/kg), whereas control rats including pair-fed (PF) and ad libitum consumption (AL) groups were given a zinc-supplemented (50.8 mg zinc/kg) diet for 4 wk. Half of the ZD rats received L-NAME (0.3 g/L in drinking water) for 3 wk starting at the wk 2 of the deficient period. Plasma zinc concentration in ZD rats was significantly lower (P < 0.05) than that of AL and PF rats. Administration of L-NAME did not alter this concentration. Intestinal zinc concentration did not differ among groups. However, metallothionein-1 (MT-1) mRNA level was significantly lower in the intestine of ZD rats than in AL or PF rats. Treatment of ZD rats with L-NAME did not affect this level. Intestinal microvascular permeability evaluated by Evans blue showed significantly higher extravasation in ZD rats than in AL rats, whereas L-NAME administration inhibited the extravasation. Expression of inducible NOS mRNA was observed in intestine of ZD but not of AL or PF rats, and there was no significant difference between ZD rats, regardless of L-NAME treatment. The activity ratio of inducible NOS to total NOS in ZD rats not receiving L-NAME was significantly higher than that in AL rats or ZD rats treated with L-NAME (P < 0.05). The number of apoptotic-positive and goblet cells in intestinal villi was significantly higher in ZD rats compared with AL or PF rats. L-NAME administration in ZD rats reversed this effect. These results indicate that inhibition of NOS ameliorates zinc deficiency-induced intestinal damage in rats.
给缺锌（ZD）大鼠注射一氧化氮合酶（NOS）抑制剂NG-硝基-L-精氨酸甲酯（L-NAME），以确定其是否能预防在这些条件下通常观察到的肠道损伤。将断奶雄性大鼠自由喂食ZD饮食（2毫克锌/千克），而包括配对喂养（PF）和随意进食（AL）组的对照大鼠则喂食补充锌（50.8毫克锌/千克）的饮食4周。从缺锌期第2周开始，一半的ZD大鼠接受L-NAME（饮用水中0.3克/升）3周。ZD大鼠的血浆锌浓度显著低于AL和PF大鼠（P<0.05）。给予L-NAME并未改变该浓度。各组肠道锌浓度无差异。然而，ZD大鼠肠道中的金属硫蛋白-1（MT-1）mRNA水平显著低于AL或PF大鼠。用L-NAME治疗ZD大鼠并未影响该水平。通过伊文思蓝评估的肠道微血管通透性显示，ZD大鼠的渗出明显高于AL大鼠，而给予L-NAME可抑制渗出。在ZD大鼠的肠道中观察到诱导型NOS mRNA的表达，而在AL或PF大鼠中未观察到，并且无论是否接受L-NAME治疗，ZD大鼠之间均无显著差异。未接受L-NAME的ZD大鼠中诱导型NOS与总NOS的活性比显著高于AL大鼠或接受L-NAME治疗的ZD大鼠（P<0.05）。与AL或PF大鼠相比，ZD大鼠肠绒毛中凋亡阳性细胞和杯状细胞的数量显著更高。在ZD大鼠中给予L-NAME可逆转这种效应。这些结果表明，抑制NOS可改善缺锌诱导的大鼠肠道损伤。
