人参皂甙对内毒素休克大鼠NO/NOS系统的影响

目的：研究人参皂甙和非选择性一氧化氮合酶(NOS)抑制剂L—硝基—精氨酸(L-NNA)对内毒素休克大鼠NO／NOS系统的影响。方法：大鼠腹腔注射大肠杆菌脂多糖(LPS，10mg／kg)后随机分为对照组、LPS组、L-NNA组与人参皂甙组，观察平均动脉压(MAP)、肌酐清除率(Ccr)、肾组织NO浓度，总NOS(tNOs)、诱导型NOS(iNOS)活性与iNOS／tNOS比值以及肾组织病理变化。结果：(1)LPS组MAP及Ccr显著降低，肾组织NO增高，tNOS与iNOS活性以及iNOS／tNOS比值升高。肾间质水肿伴炎症细胞浸润，部分小管上皮细胞变性、坏死并见管型，死亡率20％。(2)L-NNA组MAP升高，但肾功能与病理损害更著，iNOS／tNOS比值较LPS组更高，死亡率达32％。(3)人参皂甙可纠正低血压，改善肾功能及病理损害，减轻肾组织NO过度升高，tNOS与iNOS活性以及iNOS／tNOS比值均较LPS组明显下降，死亡率8％。结论：L-NNA虽能阻止LPS引起的低血压，但肾功能与病理损害恶化，死亡率增加，可能与其对结构型NOS(cNOS)的抑制较iNOS更著有关；人参皂甙可维持血压，改善肾功能，维持cNOS、抑制iNOS、调节NOS亚型的特异性作用。

Effects of Ginsenoside on the NO/NOS in a Rat Endotoxic Shock Model

Objective:To investigate the effect of Ginsenoside on the rat model of endotoxic Shock, compared with a nonselective NOS inhibitor, L-NNA.Methods:Celiac injection of lipopolysaccharide (LPS) to anaesthetized SD rats produced the rat model of endotoxic Shock. Four groups were included in the experiment: control, LPS, LPS+L-NNA and LPS+Ginsenoside. The following parameters were observed: mean arterial pressure (MAP), creatinine clearance rate (Ccr), nitric oxide (NO) concentrations in renal tissue, activities of total nitric oxide synthase (tNOS) and inducible nitric oxide synthase (iNOS) in renal tissue, renal histologic assessment.Results:Celiac injection of LPS to anaesthetized SD rats induced a significant decrease in MAP and Ccr, a significant increase of NO concentrations in renal tissue, and meanwhile elevations of tNOS and iNOS activities and the ratio of iNOS/tNOS in renal tissue. The histologic changes of renal tissue were interstitial edema with inflammatory cellular infiltration, denaturalization and necrosis in some tubular epithelia. LPS caused 20% rats death. Celiac injection of L-NNA with LPS reversed MAP significantly, however, L-NNA exacerbated the impairments of renal function and histologic damage. At the same time, L-NNA increased the ratio of iNOS/tNOS. 32% rats treated with LPS plus L-NNA died. Ginsenoside not only restored MAP, prevented the increase of NO concentrations in renal tissue, but also attenuated the impairment of renal function and renal pathological changes. Ginsenoside caused the decrease in activities of tNOS and iNOS and especially the ratio of iNOS/tNOS in renal tissue. The mortality of the rats treated with LPS was reduced to 8%. Conclusion:L-NNA prevented hypotension induced by LPS, but exacerbated the impairments of renal function and histologic damage and increased the mortality. Ginsenoside maintained blood pressure of circulation,maintained cNOS, inhibited iNOS and regulated iNOS/tNOS special effect. It was worth further investgating and discussion.