川芎嗪纳米喷雾剂对抗实验性腹腔粘连模型大鼠的最佳有效剂量

摘要

BACKGROUND:Ligustrazine can effectively prevent and treat peritoneal adhesion and adhesive ileus after surgical treatment. OBJECTIVE:To prepare Ligustrazine nanoparticle spray which is prepared to achieve sustained release and improve clinical efficacy and to explore its optimal dose for preventing experimental peritoneal adhesions in rats. METHODS:Eighty rats were randomly divided into five groups:model group, sodium hyaluronate group, high-, medium-and low-dose Ligustrazine nanoparticle groups, with 16 rats in each group. After peritoneal adhesion model was established with rasp method, model group was immediately subject to abdomen-closing, while sodium hyaluronate group and Ligustrazine nanoparticle groups received sodium hyaluronate smearing and Ligustrazine nanoparticle spray (2.5, 5, 10 mg/kg), respectively. Al rats were kil ed at 1 and 2 weeks after modeling, to observe adhesions. The adhesion score was recorded. The adhesive tissue sections were stained with hematoxylin-eosin for pathological changes. The level of transformation growth factor-β1 in peritoneal fluid of rats was detected with ELISA assay. RESULTS AND CONCLUSION:Ligustrazine Nanoparticle spray had a sustained release effect, and prolonged the duration of action of drugs, thus achieving a better anti-adhesion effect post-surgery. The medium-and high-dose Ligustrazine nanoparticle sprays exhibited better anti-adhesion effects, and improved the rise of transformation growth factor-β1 level in the peritoneal fluid. As the drug concentration is low, the intraperitoneal administration in a spray manner is preferred. Because the total dose is limited, we define the optimal effective dose as 5 mg/kg.%背景：临床应用川芎嗪防治外科治疗后腹腔粘连和粘连性肠梗阻时取得明显疗效。目的：为了达到缓释性并且提高临床疗效，将川芎嗪同纳米技术结合制备成川芎嗪纳米喷雾剂，探讨其抗大鼠实验性腹腔粘连的最佳有效剂量。方法：将80只大鼠随机分为5组：模型组、透明质酸钠组、川芎嗪纳米喷雾剂低、中、高剂量组，每组16只。以锉刀法建立腹腔粘连大鼠模型，模型组直接关腹，其余各组大鼠分别于造模后腹腔涂抹透明质酸钠凝胶、喷涂川芎嗪纳米喷雾剂2.5，5，10 mg/kg。分别于造模后1，2周处死，观察粘连情况，记录粘连得分，粘连组织切片进行苏木精-伊红染色，观察粘连组织病理改变，Elisa法测定大鼠腹腔液转化生长因子β1的水平。结果与结论：川芎嗪纳米喷雾剂具有缓释作用，延长了药物的作用时间，从而达到了更好的抗术后粘连的作用。其中以川芎嗪纳米喷雾剂中、高剂量抗粘连效果最好；川芎嗪纳米喷雾剂中、高剂量组可以对粘连模型大鼠腹腔液转化生长因子β1水平的升高有较好的改善作用。综合考虑到药物的浓度较低，给药方式为腹腔喷雾给药，因给药总量的限制，选择5 mg/kg为最佳有效的剂量。