金丝桃苷对慢性阻塞性肺疾病大鼠骨质疏松的骨代谢、生物力学的影响

Effects of hypericin on bone metabolism,biomechanics and mechanism of osteoporosis in rats with chronic obstructive pulmonary disease

目的探讨金丝桃苷对慢性阻塞性肺疾病(COPD)大鼠骨质疏松(OP)的影响及作用机制。方法用香烟联合细菌的方法构建COPD合并OP大鼠模型。将大鼠随机分为对照组、模型组(构建COPD合并OP模型)、低剂量实验组(构建COPD合并OP模型后灌胃给予50 mg·kg^(-1)金丝桃苷)、高剂量实验组(构建COPD合并OP模型后灌胃给予100 mg·kg^(-1)金丝桃苷)、阳性组(构建COPD合并OP模型后皮下注射16 U·kg^(-1)鲑降钙素),每组12只,连续给药90 d。用肺功能仪检测仪大鼠肺功能,用micro-计算机体层成像(CT)仪检测大鼠骨密度(BMD),用酶联免疫吸附试验(ELISA)实验检测大鼠血清骨代谢、炎性因子相关指标水平,用蛋白质印迹实验检测通路相关指标。结果对照组、模型组、高剂量实验组、阳性组大鼠用力肺活量(FVC)水平分别为(10.42±1.40)、(4.10±0.60)、(6.75±0.37)、(4.18±0.33)mL,BMD水平分别为(0.31±0.04)、(0.12±0.02)、(0.28±0.03)、(0.29±0.04)g·mm^(-3),骨碱性磷酸酶(BALP)水平分别为(200.04±20.03)、(80.80±6.00)、(148.16±14.23)、(173.97±23.55)U·L^(-1),白细胞介素-1β(IL-1β)水平分别为(122.60±8.70)、(695.59±74.84)、(422.41±44.86)、(527.90±39.36)pg·mL^(-1),磷酸化p38丝裂原活化蛋白激酶(p-P38)蛋白相对表达水平分别为0.99±0.11、0.36±0.05、0.79±0.08、0.36±0.04。模型组的上述指标与对照组比较,在统计学上差异均有统计学意义(均P<0.05);高剂量组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.05)。结论金丝桃苷可抑制炎性反应、改善骨代谢及生物力学。

Objective To investigate the effect and mechanism of hypericin on osteoporosis(OP)in rats with chronic obstructive pulmonary disease(COPD).Methods COPD combined with OP rat model was established by cigarette combined with bacteria.The rats were randomly divided into control group,model group(COPD combined with OP model was constructed),experimental-L group(50 mg·kg^(-1)hypericin was given by intragastric administration after constructing COPD combined with OP model),experimental-H group(100 mg·kg^(-1)hypericin was given intragastric administration after constructing COPD combined with OP model),positive group(subcutaneous injection of16 U·kg^(-1)salmon calcitonin after constructing COPD combined with OP model);each group was given 12 rats for 90 days.The lung function of rats was detected by pulmonary function apparatus;bone mineral density(BMD)was detected by micro-computed tomography(CT);serum bone metabolism and inflammatory factors were detected by enzyme-linked immunosorbent assay(ELISA);Western blot assay was used to detect the relevant indicators of the pathway.Results The levels of forced vital capacity(FVC)in control group,model group,experimental-H group and positive group were(10.42±1.40),(4.10±0.60),(6.75±0.37),(4.18±0.33)mL,respectively;BMD levels were(0.31±0.04),(0.12±0.02),(0.28±0.03),(0.29±0.04)g·mm^(-3),respectively;bone alkaline phosphatase(BALP)levels were(200.04±20.03),(80.80±6.00),(148.16±14.23),(173.97±23.55)U·L^(-1),respectively;interleukin-1β(IL-1β)levels were(122.60±8.70),(695.59±74.84),(422.41±44.86),(527.90±39.36) pg·mL^(-1),respectively;phosphorylated p38 mitogen-activated protein kinase(p-P38)protein expression levels were0.99±0.11,0.36±0.05,0.79±0.08,0.36±0.04,respectively.Compared with the control group,the above indexes in the model group had statistical significance(all P<0.05);the above indexes in experimental-H group were significantly different from those in model group(all P<0.05).Conclusion Hypericin can inhibit inflammatory response,improve bone metabolism and biomechanics.