雷公藤多甙对溃疡性结肠炎大鼠凝血功能的影响

Influence of tripterygium wilfordii polyglycoside on coagulation function of rats with ulcerative colitis

目的:观察雷公藤多甙对溃疡性结肠炎(ulcerative colitis,UC)大鼠凝血功能的影响。方法:将64只雄性清洁级SD大鼠随机分为模型组52只和正常对照组12只。正常对照组不做任何处理,模型组采用2,4-二硝基氯苯和醋酸复合法制作UC大鼠模型。于造模第19天,随机处死正常对照鼠和模型鼠各2只,确定造模成功后,将造模大鼠随机分成5组:模型对照组、肝素治疗对照组、雷公藤多甙低剂量组、雷公藤多甙中剂量组、雷公藤多甙高剂量组,每组10只。正常对照组和模型对照组不给药物,肝素治疗对照组尾静脉注射肝素钠50 U/100 g,雷公藤多甙低、中、高剂量组分别灌胃37.5 mg/kg、75 mg/kg和150 mg/kg,连续给药15 d。各组大鼠腹主动脉取血,一部分枸橼酸钠抗凝,用全自动血凝分析仪检测大鼠血浆活化部分凝血活酶时间(activated partial thromboplastin time,APTT)、凝血酶原时间(prothrombin time,PT)、纤维蛋白原(fibrinogen,FIB)水平;另一部分(ethylene diamine tetraacetic acid,EDTA)抗凝,用全自动血球分析仪检测大鼠血小板(platelet,PLT)数量。同时剖杀大鼠取结肠,观察结肠组织形态学及病理学变化。结果:大鼠PT和APTT,雷公藤多甙低[(7.18±0.22)s,(17.89±0.26)s]、中[(7.44±0.16)s,(19.87±0.46)s]和高[(7.72±0.13)s,(22.87±1.19)s]剂量组均低于正常对照组[(8.75±0.16)s,(24.79±0.77)s](P<0.05),高于模型对照组[(6.51±0.27)s,(16.82±0.42)s](P<0.05)。FIB和PLT,雷公藤多甙低[(2.39±0.12)g/L,(1050.20±28.42)×109/L]、中[(2.33±0.12)g/L,(969.60±15.36)×109/L]和高[(1.91±0.06)g/L,(907.60±14.59)×109/L]剂量组均高于正常对照组[(1.69±0.12)g/L,(840.80±26.67)×109/L](P<0.05),低于模型对照组[(3.12±0.44)g/L,(1224.80±75.06)×109/L](P<0.05)。雷公藤多甙各剂量组结肠组织炎症较模型对照组明显减轻,结肠组织形态学评分和溃疡形成分级均明显降低。结论:雷公藤多甙能延长UC大鼠PT、APTT,降低FIB、PLT,从而减轻结肠炎症反应。

Objective：To observe the influence of tripterygium wilfordii polyglycoside （TWP） on the coagulation function of rats with ulcerative colitis（UC）. Methods ：Sixty-four female clean grade Sprague-Dawley（SD） rats were randomly divided into 52 model rats and 12 normal control rats. Rats in normal control group were left intact. Rats in model group were used to establish UC rat model by a compound method of 2,4-dinitrochlorobenzene（DNCB） and acetic acid. On the 19th day,two rats were killed in normal control group and model group, respectively. After the UC rat model being established successfully, UC model rats were randomly divided into 5 groups with each group of 10 rats：model control group, heparin treatment control group,TWP low dose group,TWP moderate dose group,TWP high dose group. Rats in normal control group and model control group were not given any drugs. Heparin treatment con- trol group was injected with heparin sodium through caudal vein. TWP low dose group, moderate dose group and high dose group were administrated with TWP 37.5 mg/kg, 75 mg/kg and 150 mg/kg, respectively. Rats were given drugs for 15 days. The blood was collect- ed from abdominal aorta;one part was anticoagulated by sodium citrate to detect activated partial thromboplastin time （APTY）,pro-thrombin time （PT）, fibrinogen （FIB） using automatic blood co- agulation analyzer;another part was anticoagulated by ethylene diamine tetraacetic acid （EDTA） to detect platelet （PLT） using automatic blood cell analyzer. Moreover,all rats were killed to collect colon tissue. The morphological and pathological changes of colon tissue were observed. Results：For PT and APTT,TWP low dose group[（7.18 ± 0.22） s, （17.89 ±0.26） s] , moderate dose group [（7.44 ± 0.16） s, （19.87 ± 0.46） s] and high dose group[（7.72 ± 0.13） s, （22.87 ± 1.19） s] were lower than normal control group [（8.75 ± 0.16） s, （24.79 ± 0.77） s]（P〈0.05）,and higher than model control group[（6.51 ± 0.27） s, （16.82 ± 0.42） s]（P〈0.05）. For FIB and PLT,TWP low dose group[（2.39 ± 0.12） g/L, （1 050.20 ± 28.42） × 109/L],moderate dose group[（2.33 ± 0.12） g/L, （969.60 ± 15.36）×109/L] and high dose group[（1.91 ± 0.06） g/L, （907.60 ± 14.59） × 109/L] were higher than normal control group[（1.69 ± 0.12） g/L, （840.80 ± 26.67） × 109/L]（P〈O.05） and lower than model control group[（3.12 ± 0.44） g/L, （1 224.80 ± 75.06） × 109/L]（P〈0.05）. Compared with those of model control group, there were less inflammation and lower morphology scoring and ulcer formation grading of colon tissue in rats of drug dose groups. Conclusion ： TWP can prolong PT and APTT, and decrease FIB and PLT, thus alleviate in- flammation in colon tissues of rats infected with ulcerative colitis.