肝硬化大鼠的高动力循环：P物质的作用及其与一氧化氮的关系。

Chu C J, Lee F Y, Wang S S, Chang F Y, Tsai Y T, Lin H C, Hou M C, Wu S L, Tai C C, Lee S D

Dept. of Medicine, Veterans General Hospital-Taipei and National Yang-Ming University School of Medicine, Taiwan.

Scand J Gastroenterol. 1997 Aug;32(8):841-6. doi: 10.3109/00365529708996544.

BACKGROUND

It has been suggested that excessive formation of nitric oxide (NO) is responsible for the hyperdynamic circulation observed in portal hypertension. Substance P is a neuropeptide partly cleared by the liver and causes vasodilatation through the activation of the endothelial NO pathway. However, there are no previously published data concerning the plasma level of substance P in cirrhotic rats and its relationship to NO.

METHODS

Plasma concentrations of substance P and nitrate/nitrite (an index of NO production) were determined in control rats and cirrhotic rats with or without ascites using an enzyme-linked immununosorbent assay and a colorimetric assay, respectively. In addition, systemic and portal hemodynamics were evaluated by a thermodilution technique and catheterization.

RESULTS

Cirrhotic rats with and without ascites had a lower systemic vascular resistance (2.6 +/- 0.2 and 3.9 +/- 0.4 mmHg ml(-1) x min x 100 g body weight, respectively) and higher portal pressure (14.6 +/- 0.6 and 11.3 +/- 1.8 mmHg) than control rats (6.5 +/- 0.3 mmHg x ml(-1) x min x 100 g BW and 6.8 +/- 0.2 mmHg, respectively, P < 0.05), and cirrhotic rats with ascites had the lowest systemic vascular resistance. Plasma levels of nitrate/nitrite progressively increased in relation to the severity of liver dysfunction (control rats, 2.7 +/- 0.5 nmol/ml; cirrhotic rats without ascites, 5.6 +/- 1.3 nmol/ml; cirrhotic rats with ascites, 8.3 +/- 2.2 nmol/ml; P < 0.05). Cirrhotic rats with ascites displayed higher plasma values of substance P (57.7 +/- 5.9 pg/ml) than cirrhotic rats without ascites (37.9 +/- 3.1 pg/ml, P < 0.05) and control rats (30.1 +/- 1.0 pg/ml, P < 0.05). There was no significant difference in plasma substance P values between control rats and cirrhotic rats without ascites (P > 0.05). No correlation was found between plasma levels of substance P and nitrate/nitrite (r = 0.318, P > 0.05).

CONCLUSIONS

Excessive formation of NO may be responsible, at least partly, for the hemodynamic derangements in cirrhosis. Although substance P may not participate in the initiation of a hyperdynamic circulation in cirrhosis, it may contribute to the maintenance of the hyperdynamic circulation observed in cirrhotic rats with ascites.

背景

有研究表明，一氧化氮（NO）生成过多是门静脉高压时高动力循环的原因。P物质是一种神经肽，部分经肝脏清除，并通过激活内皮NO途径引起血管舒张。然而，此前尚无关于肝硬化大鼠血浆P物质水平及其与NO关系的公开数据。

方法

分别采用酶联免疫吸附测定法和比色法，测定对照大鼠以及有或无腹水的肝硬化大鼠血浆中P物质和硝酸盐/亚硝酸盐（NO生成指标）的浓度。此外，通过热稀释技术和导管插入术评估体循环和门静脉血流动力学。

结果

有腹水和无腹水的肝硬化大鼠的体循环血管阻力均低于对照大鼠（分别为2.6±0.2和3.9±0.4 mmHg·ml⁻¹·min⁻¹·100 g体重），门静脉压力则高于对照大鼠（分别为14.6±0.6和11.3±1.8 mmHg）（对照大鼠分别为6.5±0.3 mmHg·ml⁻¹·min⁻¹·100 g体重和6.8±0.2 mmHg，P<0.05），且有腹水的肝硬化大鼠体循环血管阻力最低。硝酸盐/亚硝酸盐的血浆水平随肝功能损害程度加重而逐渐升高（对照大鼠为2.7±0.5 nmol/ml；无腹水的肝硬化大鼠为5.6±1.3 nmol/ml；有腹水的肝硬化大鼠为8.3±2.2 nmol/ml；P<0.05）。有腹水的肝硬化大鼠血浆P物质值（57.7±5.9 pg/ml）高于无腹水的肝硬化大鼠（37.9±3.1 pg/ml，P<0.05）和对照大鼠（30.1±1.0 pg/ml，P<0.05）。对照大鼠和无腹水的肝硬化大鼠血浆P物质值无显著差异（P>0.05）。血浆P物质水平与硝酸盐/亚硝酸盐之间未发现相关性（r = 0.318，P>0.05）。