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目的:观察左旋多沙唑嗪[(-)DOX]、右旋多沙唑嗪[(+)DOX]和消旋多沙唑嗪[(±)DOX]对兔离体回肠和十二指肠收缩活动的影响,为其消化系统不良反应的发生提供实验依据。方法:制备兔离体回肠、回肠纵肌、回肠环肌和十二指肠标本各10份,各标本两端分别固定于麦氏浴槽和张力换能器。实验分4组:(-)DOX组、(+)DOX组、(±)DOX组和蒸馏水对照组。(-)DOX、(+)DOX和(±)DOX各有3种不同浓度(3、10、30μmol/L),蒸馏水为15、35、100μl。将3种浓度的(-)DOX、(+)DOX和(±)DOX及3种容量的蒸馏水分别加入浴槽中,测量3种药物对回肠、回肠纵肌和十二指肠收缩频率和幅度的影响。另外,将(-)DOX、(+)DOX、(±)DOX和蒸馏水各150μl加入浴槽,20 min后,加入卡巴胆碱20μmol/L。在给予卡巴胆碱后30 min内记录回肠环肌收缩频率和幅度。结果:3种药物均抑制回肠收缩频率。(-)DOX、(+)DOX和(±)DOX在30μmol/L浓度时,回肠收缩频率分别为(8.2±1.6)、(7.1±1.5)和(6.8±1.4)次/min,与用药前的收缩频率[(11.0±1.5)、(10.3±1.7)和(10.6±2.1)次/min]或蒸馏水的收缩频率[(10.6±1.6)次/min]相比,差异均有统计学意义(均P<0.01)。3种药物均抑制回肠纵肌收缩频率。(-)DOX、(+)DOX和(±)DOX在30μmol/L浓度时,回肠纵肌收缩频率分别为(10.1±1.5)、(9.7±2.1)和(9.0±2.2)次/min,与用药前的收缩频率[(12.9±2.8)、(13.9±1.7)和(13.0±1.8)次/min]相比,差异有统计学意义(均P<0.01)。3种药物均不影响卡巴胆碱诱发的回肠环肌收缩活动,与蒸馏水相比,差异无统计学意义(均P>0.05)。3种药物均抑制十二指肠收缩频率和收缩力。(-)DOX、(+)DOX和(±)DOX在30μmol/L浓度时,十二指肠收缩频率分别为(11.9±1.2)、(14.2±2.6)和(12.5±1.8)次/min,与用药前的收缩频率[(16.5±1.4)、(17.5±1.8)和(15.1±1.5)次/min]或蒸馏水的收缩频率[(16.0±2.2)次/min]相比,差异均有统计学意义(均P<0.01);此外,十二指肠收缩力分别为(0.75±0.44)、(0.71±0.22)和(0.87±0.58)g,与用药前收缩力[(3.81±0.66)、(4.12±0.66)和(3.96±0.74)g]或蒸馏水的收缩力[(3.87±0.70)g]相比,差异均有统计学意义(均P<0.01)。结论:多沙唑嗪及其光学异构体对回肠和回肠纵肌收缩频率及十二指肠收缩频率和幅度有显著抑制作用,其中左旋多沙唑嗪的抑制作用相对较弱。
OBJECTIVE: To observe the effects of doxazosin [(-) DOX], dexrazoxane [(+) DOX] and racemic doxazosin [(±) DOX] on ileum and duodenum Contractile activity, provide an experimental basis for the occurrence of adverse reactions of the digestive system. Methods: 10 rabbits were divided into ileum, longitudinal muscle of ileum, ileum and duodenum. The two ends of each specimen were fixed in Maxwell’s bath and tension transducer respectively. The experiment was divided into 4 groups: (-) DOX group, (+) DOX group, (±) DOX group and distilled water control group. (-) DOX, (+) DOX and (±) DOX respectively in 3 different concentration (3,10,30μmol / L), distilled water 15,35,100μl. Three kinds of DOX, (+) DOX, (±) DOX and (±) DOX and three volumes of distilled water were added into the bath respectively to measure the frequency and amplitude of contraction of ileum, ileum longitudinal muscle and duodenum influences. In addition, 150 μl of (-) DOX, (+) DOX, (±) DOX, and distilled water were added to the bath, and after 20 min, carbachol 20 μmol / L was added. The ileocortical muscle contraction frequency and amplitude were recorded within 30 min of carbachol administration. Results: All three drugs inhibited ileal contraction frequency. The ileal contraction frequency was (8.2 ± 1.6), (7.1 ± 1.5) and (6.8 ± 1.4) times / min with (-) DOX, (+) DOX and (±) DOX at 30μmol / (11.0 ± 1.5), (10.3 ± 1.7), and (10.6 ± 2.1) / min], or the contractile frequency of distilled water [(10.6 ± 1.6) times / min) All P <0.01). Three kinds of drugs inhibit the longitudinal frequency of ileum contraction. (-) DOX, (+) DOX and (±) DOX at the concentration of 30μmol / L were (10.1 ± 1.5), (9.7 ± 2.1) and (9.0 ± 2.2) The difference of systolic frequency before treatment was statistically significant (all P <0.01) compared with that of the control group [(12.9 ± 2.8), (13.9 ± 1.7) and (13.0 ± 1.8) times / min] All the three drugs did not affect carbachol-induced contractile activity of ileum annulus. Compared with distilled water, the difference was not statistically significant (all P> 0.05). All three drugs inhibited duodenal contraction frequency and contractility. (-) DOX, (+) DOX and (±) DOX in duodenum were (11.9 ± 1.2), (14.2 ± 2.6) and (12.5 ± 1.8) Compared with the systolic frequency [(16.5 ± 1.4), (17.5 ± 1.8) and (15.1 ± 1.5) times / min] or the contraction frequency of distilled water [(16.0 ± 2.2) times / min) (0.75 ± 0.44), (0.71 ± 0.22) and (0.87 ± 0.58) g respectively, which were significantly higher than those before treatment (3.81 ± 0.66, P <0.01) (4.12 ± 0.66) vs (3.96 ± 0.74) g or distilled water contractility (3.87 ± 0.70) g, respectively (all P <0.01). CONCLUSION: Doxazosin and its optical isomers have a significant inhibitory effect on the longitudinal frequency of ileum and ileum longitudinal muscle contraction and the frequency and amplitude of duodenal contraction. The inhibition of levodopa zoxazine is relatively weak.