大鼠慢性体表溃疡模型的建立与朱红膏毒效关系研究

发布时间：2018-03-15 10:01

本文选题：安全性　切入点：毒效关系　出处：《北京中医药大学》2011年硕士论文　论文类型：学位论文

【摘要】：目的 1建立一种符合临床溃疡形态,并且愈合速度较慢的大鼠慢性体表溃疡模型。 2研究朱红膏的用药安全性,指导临床安全用药。 3研究朱红膏的毒效关系,为临床用药提供依据。方法 1 SD雄性大鼠12只随机分为3组,分别为：皮肤缺损+细菌感染组(PR),皮肤缺损+埋置异物组(PW),皮肤缺损+细菌感染+埋置异物组(PRW),予以不同的体表溃疡模型造模方法,观察溃疡愈合情况,筛选最佳造模方案。 2 SD雄性大鼠66只随机分为高剂量组(38.08mg生药/kg)、中剂量组(19.04mg生药/kg)、低剂量组(9.52mg生药/kg)、基质组(凡士林)、溃疡模型组以及皮肤破损组。各给药组、基质组及溃疡模型组按筛选出的最佳方案造模,皮肤破损组以刀片刮伤方式造模。实验观察尿β-N-乙酰氨基葡萄糖苷酶(NAG)活性,尿视黄醇结合蛋白(RBP)含量及肾脏组织病理改变。 3 SD雄性大鼠80只随机分为皮肤破损组、溃疡模型组、凡士林基质组、朱红膏A～E各剂量组(剂量设置分别为：1218.56mg生药/kg,609.28mg生药/kg,304.64mg生药/kg,152.32mg生药/kg,76.16mg生药/kg)。朱红膏各剂量组、基质组及溃疡模型组按筛选出的最佳方案造模,皮肤破损组以刀片刮伤方式造模。实验观察溃疡创面愈合情况,尿视黄醇结合蛋白(RBP)含量,肉芽组织总蛋白(TP)含量,肉芽组织羟脯氨酸(Hyp)含量,肉芽组织血管内皮生长因子(VEGF)含量变化。结果 1大鼠慢性体表溃疡模型的建立实验,PRW组溃疡愈合速度明显减慢,与PR组及PW组比较有差异(P0.01),PR组与PW组比较无明显差异；且与临床溃疡在形态学上相似。 2朱红膏促进皮肤溃疡愈合的安全性研究实验,与溃疡模型组比较,朱红膏各组、凡士林基质组及皮肤破损组尿NAG活性未见明显差异(P0.05)；尿RBP含量显著升高(P0.05)；肾脏组织病理检查结果示随着用药剂量的增加,肾脏组织病变有加重趋势,与皮肤破损组比较,朱红膏高剂量组有较明显病变(P0.05),与溃疡模型组比较,朱红膏各组、凡士林基质组及皮肤破损组肾脏病变未见明显差异(P0.05)。 3朱红膏促进皮肤溃疡愈合的机制研究给药4 d,各组溃疡面积愈合情况没有差异(P0.05)；给药7d,朱红膏D、E剂量组和基质组与溃疡模型组比较,溃疡愈合速度明显较快(P0.05),朱红膏B、C剂量组愈合速度低于溃疡模型组,但其差异无统计学意义,(P0.05),随着朱红膏剂量的增加,溃疡愈合速度有减慢趋势；给药14d,朱红膏各剂量组与溃疡模型组比,溃疡愈合速度均明显较快(P0.05),但无随剂量而改变的趋势。给药7d,与溃疡模型组相比,朱红膏A剂量组RBP含量明显升高(P0.05)；朱红膏各剂量组肉芽组织TP含量均明显升高(P0.05)；朱红膏各剂量组肉芽组织Hyp含量均明显升高(P0.001)；朱红膏C～D肉芽组织VEGF含量明显升高(P0.05)。给药14d,与溃疡模型组相比,朱红膏A～D剂量组RBP含量明显升高(P0.01)；朱红膏各剂量组肉芽组织TP含量均明显升高(P0.01)；朱红膏C～E剂量组Hyp含量明显升高(P0.05)；朱红膏A～B剂量组VEGF含量明显降低(P0.01)。结论 1皮肤缺损+细菌感染+埋置异物的三种因素组合方法造模较佳。 2朱红膏19.04 mg生药/kg,用药2周可认为基本安全。 3朱红膏可显著加快溃疡创面的愈合速度。 4给药7d时,朱红膏A剂量为相对毒性剂量,B～E剂量可认为基本安全；给药14d时,朱红膏E剂量可认为安全,而大于D剂量认为有可能会引起毒性反应,为相对毒性剂量。 5给药7d、14d时,朱红膏均明显提高溃疡创面的Hyp水平和肉芽组织TP水平。 6给药7d时,朱红膏可显著增加创面肉芽组织VEGF水平,给药14d时,这种增加趋势减弱,甚至低于对照组。
[Abstract]:objective
1 to establish a chronic surface ulcer model in rats that conforms to the morphology of the clinical ulcers and has a slow healing rate.
2 to study the safety of Zhu Hong ointment and to guide the safety of clinical medication.
3 to study the toxic effect of Zhu Hong ointment and provide the basis for clinical medication.
Method
1 12 SD rats were randomly divided into 3 groups, respectively: skin defect + bacterial infection group (PR), skin defect + embedded foreign body group (PW), skin defect + bacterial infection + embedded foreign body group (PRW), to skin ulcer models with different modeling methods and healing time were observed ulcer, screening the best modeling scheme.
2 66 SD rats were randomly divided into high dose group (38.08mg crude drug /kg), medium dose group (19.04mg crude drug /kg), low dose (9.52mg crude drug /kg), medium group (Vaseline), ulcer model group and damaged skin group. In each group, medium group and ulcer model rats the best method selected, the damaged skin group was made by blade scratching mode. Experimental observation of urine beta -N- Acetylglucosaminidase activity (NAG), retinol binding protein (RBP) content and renal pathological change.
3 SD male rats were randomly divided into 80 groups of skin damage, the ulcer model group, Vaseline ointment matrix group, Zhu Hong A ~ E groups (the doses were set as follows: 1218.56mg crude drug /kg, 609.28mg crude drug /kg, 304.64mg crude drug /kg, 152.32mg crude drug /kg, 76.16mg crude drug /kg). Zhu Honggao groups, matrix group and the ulcer model group model according to the optimum scheme is selected, the damaged skin group was made by blade scratching mode. Experimental observation of ulcer healing, urinary retinol binding protein (RBP) content, total protein content, granulation tissue (TP) granulation tissue hydroxyproline (Hyp) content in granulation tissue of vascular endothelial growth factor (VEGF) content.
Result
The establishment of chronic ulcer model in 1 rats showed that ulcer healing rate in group PRW was significantly slower than that in group PR and group PW (P0.01). There was no significant difference between PR group and PW group, and it was similar to clinical ulcer in morphology.
2 Zhu Hong ointment to facilitate the experimental study on the safety of skin ulcer, ulcer compared with the model group, Zhu Hong group and vaseline ointment group, matrix damaged skin group of urinary NAG activity had no significant difference (P0.05); the contents of RBP in urine increased significantly (P0.05); the results of pathological examination of renal tissue showed increased with dose, kidney disease there is increasing trend compared with skin damage, Zhu Hong ointment had obvious lesions in high dose group (P0.05), compared with the ulcer model group, Zhu Hong group and vaseline ointment group, matrix damaged skin group showed no significant difference in renal disease (P0.05).
3 Zhu Hong ointment promoting mechanism of skin ulcer medication 4 D, no difference of area of ulcer healing (P0.05); administration of 7D, Zhu Hong extract D, E dose group and matrix group and ulcer model group, ulcer healing was faster (P0.05), Zhu Hong extract B, C dose group healing below the ulcer model group, but the difference was not statistically significant, (P0.05), with the increase of Zhu Hong ointment dose, ulcer healing rate has slowed down the trend; the administration of 14d, Zhu Hong ointment in each dose group and the ulcer model group, the ulcer healing rate was significantly faster (P0.05), but not with the dose change trend.
Administration of 7D, compared with gastric ulcer group, Zhu Hong extract A dose of RBP group were significantly increased (P0.05); the content of TP in granulation tissue of each dose group were significantly increased (Zhu Honggao P0.05); the content of Hyp in granulation tissue of each dose group of Zhu Hong ointment were significantly increased (P0.001); Zhu Hong paste C ~ D granulation tissue VEGF content significantly increased (P0.05).
Administration of 14d, compared with gastric ulcer group, Zhu Hong paste A ~ D dose group RBP significantly increased (P0.01); the content of TP in granulation tissue of each dose group were significantly increased (P0.01) Zhu Honggao; Zhu Hong paste C ~ E dose group Hyp significantly increased (P0.05); Zhu Hong plaster A ~ B dose group containing VEGF decreased (P0.01).
conclusion
1 combination of three factors, skin defect + bacterial infection + embedding foreign body, is better.
2 Zhu Hong extract 19.04 mg crude drug /kg, medication for 2 weeks can be regarded as safe.
3 Zhu Hong cream can significantly accelerate the healing speed of the ulcer wound.
4 when Zhu Hong was given 7d, the A dose of the Zhu Hong cream was relative toxic dose. The dose of B to E was considered to be basically safe. When taking 14d, the E dosage of the cream could be considered safe, while the dose greater than D dose might lead to a toxic reaction, which is a relative toxic dose.
5 at 7d and 14d, Zhu Honggao significantly increased the level of Hyp in the ulcer wound and the level of TP in the granulation tissue.
6 when 7d was given, Zhu Hong ointment could significantly increase the level of VEGF in the granulation tissue of the wound. When the drug was given to 14d, the increase trend was weakened, even lower than that of the control group.

【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R-332;R285

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