姜黄素固体分散体对镉致雄性大鼠生殖毒性的干预作用

发布时间：2018-06-16 21:12

本文选题：姜黄素 + 固体分散体　；参考：《华北理工大学》2015年硕士论文

【摘要】：目的本研究以可溶性的高分子材料聚乙烯吡咯烷酮(PVP k30)为载体将姜黄素制成固体分散体,用以提高姜黄素的生物利用度。探讨姜黄素固体分散体对镉致雄性生殖毒性的干预作用,对镉引起的雄性生殖毒性的治疗提供新的线索和思路。方法1姜黄素固体分散体的制备:以水溶性载体材料PVP k30为载体,分别制备1:2,1:4,1:6三种比例的姜黄素固体分散体,通过溶解度测定和体外溶出度测定筛选出最佳比例。用示差扫描量热分析(DSC)进行验证。2姜黄素固体分散体对镉致雄性大鼠生殖毒性的干预研究:健康的SPF级雄性SD大鼠(体重180-200g)40只,经过一周的适应性饲养,按照体重随机分为5组,分别为空白对照组,染镉组,姜黄素组(60 mg/kg),姜黄素固体分散体低剂量组(300 mg/kg)和姜黄素固体分散体高剂量组(450 mg/kg),除空白组外其余各组腹腔注射氯化镉2.0mg/kg,2天/次,染毒6次,空白对照组给予等体积的0.9%的生理盐水。染毒的同时灌胃给药,空白对照组和染镉组用等体积0.9%生理盐水灌胃。每天一次,连续给药6周。检测:组织中镉含量,附睾精子计数,睾丸组织超氧化物歧化酶(SOD)、半胱氨酸天冬氨酸蛋白酶(caspase-3)的活力和丙二醛(MDA)的水平,苏木素-伊红(HE)染色法观察睾丸组织病理切片。数据处理:采用统计学软件SPSS Statistics V17.0,数据结果均以(sx±)表示,整体组间为单因素方差分析,两两比较采用LSD分析,P0.05差异有统计学意义。结果1姜黄素制成固体分散体后,溶解度和体外溶出度明显增加,并且姜黄素与PVP k30质量比为1:4时增溶效果最佳。经DSC分析证明得到了固体分散体。2姜黄素固体分散体对镉致雄性大鼠生殖毒性的干预研究的测定结果:染镉组大鼠精子数量、活动率和SOD活力明显降低,精子畸形率和MDA水平、caspase-3含量升高,与空白对照组相比差异有统计学意义(P0.05),给药组精子数量、活动率和SOD活力升高,精子畸形率和MDA水平、caspase-3含量降低;病理切片显示,染镉组睾丸生精小管被破坏,生精细胞数目减少,给药组与之相比结构完整,高剂量的姜黄素固体分散体组更接近空白对照组。结论姜黄素具有清除自由基、抗氧化的能力,为了改善其溶解度差,生物利用度低的缺点,将其制成固体分散体。对于镉造成的雄性大鼠的生殖毒性,如精子存活率、活动率、畸形率,睾丸的氧化损伤与细胞凋亡等方面,姜黄素固体分散体有很好的治疗作用,固体分散体组的作用优于姜黄素组,表明制成固体分散体后姜黄素在体内的吸收增加,生物利用度得到改善,能够更好的发挥其药理活性。
[Abstract]:Aim in this study, curcumin was prepared into solid dispersion by using soluble polymer polyvinylpyrrolidone (PVP K 30) as carrier to improve the bioavailability of curcumin. To explore the effect of curcumin solid dispersion on male reproductive toxicity induced by cadmium and to provide new clues and ideas for the treatment of cadmium induced male reproductive toxicity. Methods (1) preparation of curcumin solid dispersion: three ratios of curcumin solid dispersion (1: 2: 1: 1: 4: 6) were prepared with water soluble carrier PVP K30 as carrier. The best proportion was obtained by solubility determination and dissolution test in vitro. The intervention of curcumin solid dispersion on cadmium induced reproductive toxicity in male rats was studied by differential scanning calorimetry (DSC). According to body weight, they were randomly divided into 5 groups: blank control group, cadmium exposed group, Curcumin group (60 mg / kg), curcumin solid dispersion (low dose group) (300 mg / kg) and curcumin solid dispersion group (high dose group) (450 mg / kg). The blank control group was given 0.9% saline of equal volume. The rats in the control group and the cadmium group were treated with 0.9% normal saline in the same volume. Once a day for 6 weeks. The contents of cadmium, the sperm count of epididymis, the activity of superoxide dismutase (SOD), caspase-3 (cysteine aspartate protease) and the level of malondialdehyde (MDA) in testis were measured. The pathological sections of testis were observed by hematoxylin and eosin (HEH) staining. Data processing: SPSS Statistics V17.0 was used, the data results were all expressed as SX 卤), the whole group was single factor ANOVA, the difference was statistically significant by LSD analysis (P0.05). Results 1 the solubility and dissolution in vitro of curcumin were significantly increased after the preparation of solid dispersion, and the solubilization effect was the best at 1:4 when the mass ratio of curcumin to PVP K30 was 1:4. The results of DSC analysis showed that the intervention of solid dispersion .2 curcumin solid dispersion on the reproductive toxicity of cadmium induced by cadmium in male rats showed that the sperm number, motility and SOD activity of cadmium exposed rats were significantly decreased. The rate of sperm malformation and the content of caspase-3 were significantly higher than those of the blank control group (P 0.05). The sperm quantity, motility and SOD activity in the administration group were increased, while the sperm deformity rate and MDA level were decreased. The testicular seminiferous tubules were destroyed and the number of spermatogenic cells decreased in the cadmium exposed group. Compared with the control group, the structure of the spermatogenic cells in the administration group was intact, and the high dose curcumin solid dispersion group was closer to the blank control group. Conclusion curcumin has the ability of scavenging free radical and antioxidation. In order to improve its poor solubility and low bioavailability, curcumin was prepared into solid dispersion. Curcumin solid dispersion has a good therapeutic effect on cadmium induced reproductive toxicity in male rats, such as sperm survival rate, motility rate, deformity rate, oxidative injury of testis and apoptosis. The effect of solid dispersion group was better than that of curcumin group, which indicated that the absorption of curcumin in vivo was increased, the bioavailability of curcumin was improved, and the pharmacological activity of curcumin was better than that of curcumin group.
【学位授予单位】：华北理工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R114

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