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大鼠胶原诱导性关节炎发展过程中血管孔隙率和关节血流量的变化。吲哚美辛和L-精氨酸甲酯的调节作用。

Changes in vascular porosity and joint blood flow during development of collagen induced arthritis in the rat. Modulation by indomethacin and L-NAME.

作者信息

Andersson S E, Ekström G M

机构信息

Department of Pharmacology, Astra-Draco AB, Lund, Sweden.

出版信息

J Rheumatol. 1997 Nov;24(11):2188-95.

PMID:9375882
Abstract

OBJECTIVE

To investigate changes in regional blood flows (RBF) and vascular porosity during the early phase of the autologous collagen II induced arthritis model (CIA) in rats and the possible influence of indomethacin and nitric oxide (NO) synthase on these variables.

METHODS

RBF was measured with the microsphere method and vascular porosity by determination of extravasation of radiolabeled albumin.

RESULTS

Onset of arthritis was associated with a rapid increase in vascular porosity in the knee. In ankles and paws this increase was somewhat slower in onset, but progressed during the course of the study. Acute treatment with indomethacin reduced albumin extravasation in the knees, but had no effect in the ankles or paws. Similarly, chronic indomethacin treatment also had no effect on the arthritic score. Serum levels of nitrite/nitrate did not change markedly during the development of CIA, and NO synthase inhibition did not affect the vascular porosity. The changes in RBF were relatively modest. In most tissues the total RBF increased with increasing tissue weight. Pretreatment with indomethacin reduced RBF in the paws, but not in the periarticular tissue.

CONCLUSION

The development of CIA is characterized by a marked rise in vascular porosity in affected joints, but the changes in RBF are much smaller and nonpersistent. The leakiness seems to be insensitive to the modulation of RBF and the responses in the knee show different characteristics compared to those in the ankle/paw.

摘要

目的

研究大鼠自体Ⅱ型胶原诱导性关节炎模型(CIA)早期区域血流(RBF)和血管孔隙率的变化,以及吲哚美辛和一氧化氮(NO)合酶对这些变量的可能影响。

方法

采用微球法测量RBF,通过测定放射性标记白蛋白的外渗来测量血管孔隙率。

结果

关节炎的发作与膝关节血管孔隙率的快速增加有关。在踝关节和爪子中,这种增加的起始稍慢,但在研究过程中有所进展。吲哚美辛急性治疗可减少膝关节白蛋白外渗,但对踝关节或爪子没有影响。同样,吲哚美辛慢性治疗对关节炎评分也没有影响。在CIA发展过程中,血清亚硝酸盐/硝酸盐水平没有明显变化,NO合酶抑制也不影响血管孔隙率。RBF的变化相对较小。在大多数组织中,总RBF随着组织重量的增加而增加。吲哚美辛预处理可降低爪子中的RBF,但对关节周围组织没有影响。

结论

CIA的发展特征是受累关节的血管孔隙率显著升高,但RBF的变化要小得多且不持久。渗漏似乎对RBF的调节不敏感,并且膝关节的反应与踝关节/爪子的反应表现出不同的特征。

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