脂多糖对离体培养大鼠血管平滑肌细胞增殖的影响

EFFECT OF LIPOPOLYSACCHARIDE ON THE PROLIFERATION OF RAT VSMCs IN VITRO

本研究观察到１０－７～１０－５ｋｇ／Ｌ脂多糖（ｌｉｐｏｐｏｌｙｓａｃｈａｒｉｄｅ，ＬＰＳ）可显著促进血管平滑肌细胞（ＶＳＭＣ）的增殖及ＤＮＡ的合成（Ｐ＜００５）。５×１０－４～１０－３ｋｇ／ＬＬＰＳ却抑制ＶＳＭＣ的增殖及ＤＮＡ的合成，降低其活力（Ｐ＜００１），并呈时间依赖效应。一氧化氮合酶抑制剂ＮＮｉｔｒｏＬＡｒｇｉｎｉｎｅ（ＬＮＮＡ）可拮抗ＬＰＳ的抑制作用。大剂量ＬＰＳ作用组ＶＳＭＣ上清液中一氧化氮（ＮＯ）代谢产物ＮＯ－３和ＮＯ－２的含量与对照组相比显著增加（Ｐ＜００１），４８ｈ组比２４ｈ组增加９１％，７２ｈ组比４８ｈ组增加４５％；同时，诱导性一氧化氮合酶（ｉｎｄｕｃｔｉｖｅｎｉｔｒｉｃｏｘｉｄｅｓｙｎｔｈａｓｅ，ｉＮＯＳ）免疫组化染色呈阳性。结果表明，低浓度ＬＰＳ促进ＶＳＭＣ增殖和ＤＮＡ合成，而高浓度ＬＰＳ却明显抑制ＶＳＭＣ增殖和ＤＮＡ合成，降低其活力。这种抑制作用可能与ＬＰＳ诱导ＶＳＭＣ产生的ＮＯ有关。

In cultured vascular smooth muscle cells(VSMCs) of SD rat, it was found that 1×10 -7 ～1×10 -5 kg/L lipopolysaccharide(LPS) markedly stimulated proliferation and DNA synthesis of VSMCs in a dose dependent manner ( P <0 05). A time dependent marked inhibition in proliferation, DNA synthesis and viability of VSMCs ( P <0 01)could be obtained by 5×10 -4 ～10 -3 kg/L LPS. The inhibitory effect of LPS could be prevented by L NNA, which reduced NO production by inhibiting NOS. NO - 3and NO - 2of LPS group markedly increased( P <0 01): 48 h group vs 24 h group increased by 9 1%, 72 h group vs 48 h group increased by 4 5%. When 5×10 -4 ～10 -3 kg/L LPS was added, positive immunohistochemical staining of inductive nitric oxide synthase could be observed. These results suggest that LPS of low dose stimulated the proliferation and the DNA synthesis of VSMCs, while LPS of high dose markedly inhibited them probably due to the increased NO production.