枸杞多糖通过下调Calpain-1蛋白表达改善糖尿病大鼠血管内皮依赖性舒张功能作用研究

Lycium Barbarum Polysaccharide Improves Endothelium-Dependent Vascular Relaxation in Diabetic Rats by Down-Regulating the Calpain-1 Protein Expression CHEN Wei-ying1，HE Yuan1，

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DOI：10.7661/j.cjim.20231107.308

中文关键词: 糖尿病血管舒张功能枸杞多糖一氧化氮内皮型一氧化氮内酶 Calpain-1 中药提取物

英文关键词:diabetes vascular relaxation lycium barbarum polysaccharides nitric oxide endothelial nitric oxide synthase Calpain-1 Chinese herbal extracts

基金项目:酒泉市科学技术局项目（No.2022CA1004）;甘肃省药品监督管理局项目（No.2022GSMPA0062）;国家自然科学基金资助项目（No.81960673）

作者	单位
陈卫英;何元;唐富天;陈晓梅	1.酒泉市药品检验检测中心（甘肃 735000）,2.兰州大学第二医院心内科（兰州 730030）,3.甘肃省第三人民医院儿科（兰州 730000）

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中文摘要:

目的研究枸杞多糖（LBP）对糖尿病大鼠血管舒张功能障碍的改善作用及机制。方法腹腔注射给予8周龄雄性SD大鼠链脲佐菌素[STZ，50 mg/ （kg·d），连续5天]建立糖尿病模型。将24只血糖高于15 mmol/L的大鼠随机分为STZ组、LBP高剂量组和LBP低剂量组，每组8只。另用8周龄雄性SD大鼠作为Control组。LBP高剂量组和LBP低剂量组分别灌胃给予LBP[60、30 mg/（kg·d）]，连续12周。实验结束后测定大鼠血管内皮依赖性和非依赖性舒张功能，全血中葡萄糖含量，血清中总胆固醇（TC）、甘油三酯（TG）和一氧化氮（NO）含量，血管中内皮型一氧化氮内酶活性（eNOS）和Calpain活性，血管中eNOS和Calpain-1蛋白表达。结果与Control组比较，STZ组大鼠血管内皮依赖性舒张功能明显障碍，最大舒张百分率只有Control组的45%。与Control组比较，STZ组血糖、TC、TG水平及Calpain活性、蛋白表达升高（P＜0.01），NO含量、eNOS活性和蛋白表达降低（P＜0.01）。与STZ组比较，LBP高、低剂量组可改善大鼠内皮依赖性血管舒张，同时血糖、Calpain活性、蛋白表达降低，NO含量、eNOS活性和蛋白表达升高（P＜0.05，P＜0.01）。结论 LBP能够改善糖尿病大鼠血管内皮依赖性舒张功能，其机制可能与下调Calpain-1表达，进而提高eNOS活性和增加NO含量有关。

英文摘要:

Objective To study the effect and mechanism of Lycium barbarum polysaccharide （LBP） on the dysfunction of vascular relaxation in diabetic rats. Methods The diabetes model was established by intraperitoneal injection of streptozotocin （STZ， 50 mg·kg-1·d-1，for 5 consecutive days） into 8-week old male SD rats. Totally 24 rats with blood glucose levels higher than 15 mmol/L were randomly divided into STZ group，LBP high-dose group，and LBP low-dose group. Additionally，8-weekold male SD rats were used as the Control group. The LBP high-dose group and LBP low-dose group were given LBP （60 and 30 mg·kg-1·d-1） by gavage for 12 consecutive weeks. After the experiment，both the endothelium dependent and non-dependent vascular relaxation，the content of glucose in whole blood，the content of total cholesterol （TC），triglyceride （TG） and nitric oxide （NO） in serum，the activities of endothelial form of NO synthase （eNOS） and calpain and the protein expressions of eNOS and Calpain-1 in blood vessels were measured. Results Compared with the Control group，the endothelium dependent vascular relaxation of the rats in STZ group was significantly impaired，with the maximum relaxation percentage of approximately 45% of the Control group. In addition，the levels of glucose，TC and TG，the activity of Calpain and the protein expression of Calpain-1 in STZ group increased （P＜0.01） and the content of NO and the activity and protein expression of eNOS decreased （P＜0.01）. Compared with the STZ group，LBP high and low dose group improved endothelium-dependent vascular relaxation of rats. LBP of both doses reduced glucose level，Calpain activity and Calpain-1 protein expression，increased NO content and eNOS activity and protein expression（P＜0.05，P＜0.01）. Conclusion LBP improves the endothelium-dependent vascular relaxation in diabetic rats through down-regulation of Calpain-1 expression，thus increasing eNOS activity and NO content.

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