论文部分内容阅读
前交报告了磺胺类利尿剂的利尿作用与在大鼠体内的代谢特点。本研究系继这个工作之后进行的离体大鼠腎切片的实验,目的在于观察体外腎組織轉运这类化合物的某些特点,及其与化合物利尿作用间的联系。实驗按Cross和Taggart研究兔腎切片摄聚对氨基马尿酸(PAH)的方法进行,用Warburg组織呼吸器温孵,同时观察腎切片耗氧量(Qo_2)。以s/M值(温孵后药物在切片与介液中浓度之比)表示腎切片摄聚药物的能力。测得的s/M值双氫氯噻嗪(HCT)平均为9.34±0.28,PAH为7.17±1.23。二者的s/M值在25℃时均此37℃时的高。其最适pH分別为7.8及8.0。乏氧环境抑制HCT及氯噻嗪(CT)的s/M值;醋酸刺激HCT在腎的积聚;半胱氨酸則无作用。DNP(2.5××10~(-5)M)和氰化钠(50—100×10~(-5)M)均抑制PAH、CT及HCT的s/M值。加入15倍于底物浓度的碘呲啦啥或青霉素亦能抑制HCT的s/M值(此时組織耗氧量不变)。这些結果提示HCT类化合物的腎脏轉运机制与PAH、青霉素及碘呲啦啥等可能相同。此外,还比較了8个磺胺类化合物的s/M值,其中HCT-55(5-氯双氫氯噻嗪)、HCT、HFT(三氟甲基双氫噻嗪)及CT-S(Benzthiazide)等利尿作用較强者,s/M值亦較高。DSA、CT及HCT-18等利尿作用较弱(或没有利尿作用),s/M值亦较低。大鼠肝及腎切片摄聚CT-S的能力相同,但肝切片摄聚HCT的能力远不及腎切片。
Pre-reported sulfa diuretic diuretic effect and metabolic characteristics in rats. In this study, following the work of rat kidney sections after the experiment, the purpose is to observe some of the characteristics of renal tubular transport in vitro compounds, and its relationship with the diuretic effect of compounds. Cross-Tag and Taggart were used to study the method of poly-p-aminopurine (PAH) in rabbit kidney sections. Warburg tissue respirators were used to incubate and observe the oxygen consumption (Qo_2) of kidney sections. The s / M value (the ratio of drug concentration in the section to the medium after incubation) indicates the ability of the kidney section to agglutinate the drug. The measured s / M hydrochlorothiazide (HCT) averaged 9.34 ± 0.28 and PAH was 7.17 ± 1.23. Both s / M values were high at 37 ° C at 25 ° C. The optimum pH was 7.8 and 8.0 respectively. Hypoxia inhibited HCT and chlorothiazide (CT) s / M values; acetic acid stimulated the accumulation of HCT in the kidney; cysteine had no effect. DNP (2.5 × 10 ~ (-5) M) and sodium cyanide (50 ~ 100 × 10 ~ (-5) M) inhibited the s / M values of PAH, CT and HCT. Adding iodine at 15 times the substrate concentration or penicillin also inhibits HCT s / M values (at this time the tissue oxygen consumption unchanged). These results suggest that the mechanism of renal transport of HCT compounds may be the same as that of PAH, penicillin and iodine. In addition, the s / M values of eight sulfonamides were also compared, including diuretic such as HCT-55 (hydrochlorothiazide), HCT, HFT (trihydrobenzothiazide) and CT-S Strong role, s / M values are higher. DSA, CT and HCT-18 and other diuresis was weak (or no diuretic effect), s / M values are also lower. The ability of rat liver and kidney sections to capture CT-S was the same, but the ability of liver sections to capture HCT was far less than that of kidney sections.