本文選題：安全性　切入點(diǎn)：毒效關(guān)系　出處：《北京中醫(yī)藥大學(xué)》2011年碩士論文　論文類型：學(xué)位論文

【摘要】：目的 1建立一種符合臨床潰瘍形態(tài),并且愈合速度較慢的大鼠慢性體表潰瘍模型。 2研究朱紅膏的用藥安全性,指導(dǎo)臨床安全用藥。 3研究朱紅膏的毒效關(guān)系,為臨床用藥提供依據(jù)。 方法 1 SD雄性大鼠12只隨機(jī)分為3組,分別為：皮膚缺損+細(xì)菌感染組(PR),皮膚缺損+埋置異物組(PW),皮膚缺損+細(xì)菌感染+埋置異物組(PRW),予以不同的體表潰瘍模型造模方法,觀察潰瘍愈合情況,篩選最佳造模方案。 2 SD雄性大鼠66只隨機(jī)分為高劑量組(38.08mg生藥/kg)、中劑量組(19.04mg生藥/kg)、低劑量組(9.52mg生藥/kg)、基質(zhì)組(凡士林)、潰瘍模型組以及皮膚破損組。各給藥組、基質(zhì)組及潰瘍模型組按篩選出的最佳方案造模,皮膚破損組以刀片刮傷方式造模。實(shí)驗(yàn)觀察尿β-N-乙酰氨基葡萄糖苷酶(NAG)活性,尿視黃醇結(jié)合蛋白(RBP)含量及腎臟組織病理改變。 3 SD雄性大鼠80只隨機(jī)分為皮膚破損組、潰瘍模型組、凡士林基質(zhì)組、朱紅膏A～E各劑量組(劑量設(shè)置分別為：1218.56mg生藥/kg,609.28mg生藥/kg,304.64mg生藥/kg,152.32mg生藥/kg,76.16mg生藥/kg)。朱紅膏各劑量組、基質(zhì)組及潰瘍模型組按篩選出的最佳方案造模,皮膚破損組以刀片刮傷方式造模。實(shí)驗(yàn)觀察潰瘍創(chuàng)面愈合情況,尿視黃醇結(jié)合蛋白(RBP)含量,肉芽組織總蛋白(TP)含量,肉芽組織羥脯氨酸(Hyp)含量,肉芽組織血管內(nèi)皮生長因子(VEGF)含量變化。 結(jié)果 1大鼠慢性體表潰瘍模型的建立實(shí)驗(yàn),PRW組潰瘍愈合速度明顯減慢,與PR組及PW組比較有差異(P0.01),PR組與PW組比較無明顯差異；且與臨床潰瘍在形態(tài)學(xué)上相似。 2朱紅膏促進(jìn)皮膚潰瘍愈合的安全性研究實(shí)驗(yàn),與潰瘍模型組比較,朱紅膏各組、凡士林基質(zhì)組及皮膚破損組尿NAG活性未見明顯差異(P0.05)；尿RBP含量顯著升高(P0.05)；腎臟組織病理檢查結(jié)果示隨著用藥劑量的增加,腎臟組織病變有加重趨勢,與皮膚破損組比較,朱紅膏高劑量組有較明顯病變(P0.05),與潰瘍模型組比較,朱紅膏各組、凡士林基質(zhì)組及皮膚破損組腎臟病變未見明顯差異(P0.05)。 3朱紅膏促進(jìn)皮膚潰瘍愈合的機(jī)制研究給藥4 d,各組潰瘍面積愈合情況沒有差異(P0.05)；給藥7d,朱紅膏D、E劑量組和基質(zhì)組與潰瘍模型組比較,潰瘍愈合速度明顯較快(P0.05),朱紅膏B、C劑量組愈合速度低于潰瘍模型組,但其差異無統(tǒng)計(jì)學(xué)意義,(P0.05),隨著朱紅膏劑量的增加,潰瘍愈合速度有減慢趨勢；給藥14d,朱紅膏各劑量組與潰瘍模型組比,潰瘍愈合速度均明顯較快(P0.05),但無隨劑量而改變的趨勢。 給藥7d,與潰瘍模型組相比,朱紅膏A劑量組RBP含量明顯升高(P0.05)；朱紅膏各劑量組肉芽組織TP含量均明顯升高(P0.05)；朱紅膏各劑量組肉芽組織Hyp含量均明顯升高(P0.001)；朱紅膏C～D肉芽組織VEGF含量明顯升高(P0.05)。 給藥14d,與潰瘍模型組相比,朱紅膏A～D劑量組RBP含量明顯升高(P0.01)；朱紅膏各劑量組肉芽組織TP含量均明顯升高(P0.01)；朱紅膏C～E劑量組Hyp含量明顯升高(P0.05)；朱紅膏A～B劑量組VEGF含量明顯降低(P0.01)。 結(jié)論 1皮膚缺損+細(xì)菌感染+埋置異物的三種因素組合方法造模較佳。 2朱紅膏19.04 mg生藥/kg,用藥2周可認(rèn)為基本安全。 3朱紅膏可顯著加快潰瘍創(chuàng)面的愈合速度。 4給藥7d時(shí),朱紅膏A劑量為相對毒性劑量,B～E劑量可認(rèn)為基本安全；給藥14d時(shí),朱紅膏E劑量可認(rèn)為安全,而大于D劑量認(rèn)為有可能會(huì)引起毒性反應(yīng),為相對毒性劑量。 5給藥7d、14d時(shí),朱紅膏均明顯提高潰瘍創(chuàng)面的Hyp水平和肉芽組織TP水平。 6給藥7d時(shí),朱紅膏可顯著增加創(chuàng)面肉芽組織VEGF水平,給藥14d時(shí),這種增加趨勢減弱,甚至低于對照組。
[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.

【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R-332;R285

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