穿心莲内酯新型载药系统抗炎作用及其机制研究

【作者】 杜红；

【导师】 牛欣； 冯前进；

【作者基本信息】 北京中医药大学 ， 中西医结合基础， 2005， 硕士

【摘要】 本研究旨在探讨穿心莲内酯 W 制剂的抗炎作用特点以及抗炎机制,通过与穿心莲内酯片剂进行抗炎作用对比研究,评估 W 制剂的抗炎作用,并验证 W 制剂的剂型优势。通过 W 制剂对各种炎症介质的作用,阐述其可能的抗炎机制,有实验研究发现:1 W 制剂与片剂对不同炎症模型的抗炎作用对比研究 对蛋清所致大鼠足趾肿胀实验的观察,得出:W 制剂大、中、小剂量组均能够明显抑制蛋清所致的大鼠足爪肿胀度。起效快,在给药后 0.5h 即能达到明显的抑制效果;药效持续时间长,可持续到 8h 以上。作用效果非常明显,与空白组相比,W制剂大、中、小三个剂量组在各个时段均有极显著的效果,(P<0.01)。而穿心莲内酯片剂组虽然抗炎作用也很明显(与空白组比较 P<0.01),但较 W 制剂作用强度弱,二者有很显著的差异(P<0.01)。说明其对炎症过程中的局部肿胀有很好的抑制作用。 二甲苯所致小鼠耳廓肿胀实验结果显示,在二甲苯所致的小鼠耳肿胀的炎症模型中,W 制剂显示出良好的抗炎作用,与空白组相比,有极显著的差异(P<0.01)。而穿心莲内酯片剂组在此炎症模型中,几乎没有体现出抗炎作用(P>0.05)。说明穿心莲内酯 W 制剂能够很好的抑制毛细血管通透性增强。 醋酸所致腹腔毛细血管渗出实验表明:W 制剂有明显的抑制醋酸所致毛细血管通透性增高的作用,大、中、小剂量组与空白组相比,差异极显著(P<0.01)。片剂组虽然也有明显的抑制毛细血管通透性增高的作用(与空白组相比,P<0.01),但其抑制率仅达到 34.82%,与阳性药和 W 制剂三剂量相比,均有极显著差异(P<0.01)。也说明 W 制剂有极强的抑制毛细血管通透性增强的作用。 对小鼠棉球肉芽肿实验的观察得出以下结论:W 制剂有较强的抑制肉芽增生的作用,其中,中剂量组抑制效果最为明显,抑制率达到 30.99%,小剂量组与大剂量组效果较中剂量组差,抑制率分别为 23.84%和 23.47%。穿心莲内酯片剂组的抑制率最差,仅为 16.39%。说明 W 制剂在一定程度上也可以抑制慢性炎症的发展。2 W 制剂和片剂对大鼠角叉菜胶气囊炎模型抗炎作用的对比研究 通过对大鼠角叉菜胶气囊炎模型炎症渗出液量、炎症渗出液中白细胞游走数以及蛋白质含量的测定得出以下结论:对于炎症渗出液的量的影响,穿心莲内酯 W 制剂显示出明显的抑制作用。其中,小剂量组与空白组相比差异显著,(P<0.05),中、大剂量组则差异更显著 P<0.01。从结果中还可以看出,对于炎症渗出液的抑制作用,W 制剂弱于阳性要组,但要比穿心莲内酯片剂组要强,其中,W 大剂量组于片剂组相比较,抑制作用有显著差异(P<0.05)。对于对炎症过程中白细胞游走的影响,W制剂也显示出了很好的抑制作用,与空白组相比有统计学意义,其中中剂量组差异显著,P<0.05,大剂量组差异极显著,P<0.01。与片剂相比,W 制剂的作用也要略强于片剂,但差异不显著。对于炎症渗出液中蛋白质的含量,W 中、大组的抑制蛋白质渗出的作用极显著(P<0.01),片剂与 W 小剂量组也有明显的抑制蛋白质渗出的作更多还原

【Abstract】 This article is to study and research the anti-inflammatory action and mechanisms ofandrographolide W. By contrasting to andrographolide pellet, to appraisal the effect andauthenticate the ascendancy of andrographolide W. By researching the action ofandrographolide W to mediators of inflammation, explain the potential anti-inflammatorymechanisms.1 The anti-inflammatory actions of Andrographolide W and pellet to different models Researching the experimentation of albumen leaded forced foot in rats, discovered thatall three doses of W can inhibit the swelling degree. Andrographolide W can produce effectjust 30min after administration and the effection can continue more than 8 hours. Contrastto the control group, W have the distinguished effection (P<0.01). Andrographolide pellethas anti-inflammatory action (contrast to control group P<0.01), but the action is muchinferior than that of andrographolide W. The above conclusions explain that W can inhibitthe local swelling degree during inflammatory. Researching the experimentation of xylene leaded forced ear in mice, discovered thatandrographolide W has market anti-inflammatory action, contrast with control group, theeffect of anti-inflammatory action displays evident difference(P<0.01). However,andrographolide pellet has almost no effect in this model(P>0.05). Explaining thatandrographolide W can inhibit the intensification of capillary permeability. The experiment of HAC leaded capillary permeability intension in mice indicate: Wcan inhibit the intension of capillary permeability leaded by HAC obviously, contrast tocontrol group, P<0.01. Andrographolide pellet can also inhibit the intension, but the degreeof inbibition is much lower than W. This research is also explains that andrographolide Whas strong effect of inhibition the capillary permeability intensification. The experiment of granuloma leaded by planted cotton ball in mice can arrive thefollowing conclusion: andrographolide W has strong effect of inhibiting the hyperplasia,the middle dose grop has the most perfect action, the degree of inhibition arrive to 30.99%,the degree of inhibition of small and big doses each are 23.84% and 23.47%. Theinhibition ratio of andrographolide pellet is worst, just 16.39%. The above conclusionexplains that W can inhibit the chronic inflammation in a distance.2 The anti-inflammatory actions of Andrographolide W and pellet to CAR leaded inflammation In this research we observe the diffusate amout and the WBC amout, pr content indiffusate. We get the following conclusion: andrographolide W can obviously inhibit thediffusate amout. Contrast to the control group, the small group P<0.05, the effects ofmiddle and big dose groups are much obvious, P<0.01. In this conclusion, we can alsodiscover that to the inhibit effect of diffusate, W is weaker than Asp group but strongerthan andrographolide pellet group. To the WBC amout in inflammatory, andrographolideW displays perfect inhibit action. Contrast with the control group, the difference is obvious.Among them, the middle dose P<0.05, the big dose P<0.01. Contrast to theandrographolide pellet group, the effect of W is a little better. To the content of pr indiffusate, the middle and big dose groups display obvious effection, P<0.01. The smalldose and pellet groups also have inhibit effection, P<0.05. Contrast to the pellet group, theactions of middle group and big group are better.3 The approach to the anti-inflammatory mechanisms of andrographolide W Determining the amount of PGE2, LTB4, TNF-α,IL-1β,IL-6,IL-8 by immunitymeans, we get the following conclusions: The conclusion of the researching of PGE2 and LTB4 display: the effection to PGE2 isstronger than to LTB4, all the three doses of andrographolide W can degrade the content ofPGE2 in diffusate, P<0.01. To the influence to LTB4, the small dose of W contrast with thecontrol group has no obvious difference, the middle and big groups can degrade theamount of LTB4 in diffusate (P<0.01).The conclusion of the research of cell factors display: andrographolide W has the besteff更多还原