缺氧时培养的心内膜内皮细胞内皮素自分泌调节的探讨

A STUDY OF ENDOTHELIN1 AUTOCRINE FROM CULTURED ENDOCARDIAL ENDOTHELIAL CELLS UNDER HYPOXIA

本实验观察缺氧对心内膜内皮细胞（ＥＥＣ）内皮素－１（ＥＴ－１）分泌的影响。传代培养的新生小牛右心室ＥＥＣ的ＥＴ－１免疫组织化学显色强阳性。采用放免测定发现ＥＥＣ可向培养液中分泌ＥＴ－１，其分泌速度与细胞密度呈线性负相关（ｒ＝－０．９５４２，Ｐ＜０．００１），与温育时间呈指数负相关（ｒ＝－０．９９８，Ｐ＜０．００１）。０％Ｏ２缺氧６～１２ｈ后，ＥＥＣ的ＥＴ－１分泌约增加１倍（Ｐ＜０．００１）。无论在常氧还是缺氧情况下，硝普钠抑制ＥＥＣ的ＥＴ－１分泌，而ＮＯ合酶抑制剂ＬＮＡ则促进ＥＴ－１分泌。上述结果表明：ＥＥＣ可能通过分泌ＥＴ－１调节心脏功能，内源性ＮＯ抑制ＥＴ－１分泌；

The endocardial ednothelium is an important modulator in the regulation of cardiac function. In this experiment, endothelin1(ET1) secretion by cultured newborn bovine endocardial endothelial cells (EEC) and the effects of hypoxia were investigated. Immunohistochemical staining with ET1 antibody showed ET1 in passaged EEC was positive. ET1 released from EECs to medium was measured with radioimmunoassay, the rate of ET1 release was negative correlative to cell density and incubating duration (r=-09542 and -0988 respectively, P<0001). After 6 h to 12 h incubation in hypoxia (0% O2), the rate of ET1 release increased about 2 folds (P<0001). Sodium nitroprusside inhibited ET1 release while NO synthase inhibitor Lnitroarginine promoted ET1 release by EECs either under normoxia or hypoxia. The present findings indicate that by the release of ET1, EEC may play an important role in modulating the subjacent myocardium and downstream pulmonary arterial vasculature, while endogenous NO may inhibit the releave of ET1. Accordingly, hypoxia stimutates ET1 release by inhibiting NO synthase, which may be involved in the development of hypoxic pulmonary artery hypertension and right ventricular hypertrophy.