首页|闹羊花毒素Ⅲ介导氧化应激途径对创伤后骨关节炎大鼠软骨损伤的影响

闹羊花毒素Ⅲ介导氧化应激途径对创伤后骨关节炎大鼠软骨损伤的影响

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目的 探讨闹羊花毒素Ⅲ对创伤后骨关节炎大鼠软骨损伤的影响及其作用机制.方法 将SD大鼠随机分为假手术组、模型组(根据交叉韧带切断法建模)、低剂量实验组(建模后灌胃给予0.12 mg·kg-1闹羊花毒素Ⅲ)、高剂量实验组(建模后灌胃给予0.24 mg·kg-1闹羊花毒素Ⅲ)、阳性药物组(建模后灌胃给予2 mL/100 g的硫酸氨基葡萄糖),每组10只大鼠,连续灌胃28 d后,心脏采血并处死大鼠取软骨组织备用.以Mankin's评分法分析各组大鼠软骨组织情况,以蛋白质印迹法检测相关蛋白的表达水平,以酶联免疫吸附测定(ELISA)法检测大鼠血清骨形成指标及软骨组织中相关因子表达水平,以试剂盒法检测氧化应激相关指标的表达水平.结果 假手术组、模型组、低剂量实验组、高剂量实验组和阳性药物组的Mankin's评分分别为(0.10±0.30)、(5.30±0.46)、(4.00±0.63)、(3.10±0.54)和(1.50±0.81)分,骨钙素(BGP)水平分别为(10.25±0.77)、(2.39±0.34)、(4.87±0.27)、(7.99±0.51)和(8.55±0.71)ng·mL-1,裂解的胱天蛋白酶-3(Cl-caspase-3)蛋白相对表达水平分别为0.25±0.02、0.86±0.06、0.65±0.05、0.47±0.04 和 0.33±0.03,超氧化物歧化酶(SOD)活性分别为(109.07±7.51)、(60.24±5.73)、(67.99±4.73)、(76.16±8.84)和(80.11±3.96)U·mg-1,核转录因子 E2 相关因子(Nrf2)蛋白相对表达水平分别为 1.03±0.08、0.33±0.04、0.43±0.05、0.75±0.10 和0.74±0.09,血红素加氧-1(HO-1)蛋白相对表达水平分别为0.88±0.08、0.27±0.04、0.39±0.04、0.56±0.10 和 0.58±0.06;模型组的上述指标与假手术组比较,低、高剂量实验组的上述指标分别与模型组比较,低剂量实验组的上述指标与高剂量实验组比较,在统计学上差异均有统计学意义(均P<0.05).结论 闹羊花毒素Ⅲ可能通过激活Nrf2/HO-1通路,抑制氧化应激、炎性反应、调节骨代谢,改善创伤后骨关节炎大鼠软骨损伤.
Effects of Rhodojaponin Ⅲ mediated oxidative stress pathway on cartilage injury in rats with post-traumatic osteoarthritis
Objective To investigate the effects of Rhodojaponin Ⅲ on cartilage injury in post-traumatic osteoarthritis rats and its mechanism.Methods SD rats were randomly divided into sham operation group,model group(based on cruciate ligamentectomy),low dose experimental group(after modeling,0.12 mg·kg-1 Rhodojaponin Ⅲ was given by intragastric administration),high dose experimental group(after modeling,0.24 mg·kg-1 Rhodojaponin Ⅲ was given by intragastric administration),positive drug group(2 mL/100 g glucosamine sulfate was given intragastric administration after modeling).Ten rats in each group were given continuous intragastric administration for 28 days,blood was collected from the heart,and cartilage tissue was taken from the rats.Mankin's score method was used to analyze the cartilage tissue of rats in each group,Western blot method was used to detecte the proteins level,enzyme-linked immunosorbent assay(ELISA)test was used to detect the expression level of serum bone formation indexes and related factors in cartilage tissue,and kit method was used to detect the expression of oxidative stress related indexes.Results The Mankin's scores of sham operation group,model group,low dose experimental group,high dose experimental group and positive drug group were 0.10±0.30,5.30±0.46,4.00±0.63,3.10±0.54 and 1.50±0.81;bone gla protein(BGP)level were(10.25±0.77),(2.39±0.34),(4.87±0.27),(7.99±0.51)and(8.55±0.71)ng·mL-1;the expression levels of cleaved cysteine aspartate proteinase-3(Cl-caspase-3)protein were 0.25±0.02,0.86±0.06,0.65±0.05,0.47±0.04 and 0.33±0.03;superoxide dismutase(SOD)activity were(109.07±7.51),(60.24±5.73),(67.99±4.73),(76.16±8.84)and(80.11±3.96)U·mg-1;the protein levels of nuclear transcription factor E2 related factors(Nrf2)were 1.03±0.08,0.33±0.04,0.43±0.05,0.75±0.10 and 0.74±0.09;heme oxygen-1(HO-1)protein expression levels were 0.88±0.08,0.27±0.04,0.39±0.04,0.56±0.10 and 0.58±0.06,respectively.Model group compared with sham operation group,low dose experimental group,high dose experimental group compared with model group;low dose experimental group compared with high dose experimental group,the differences of the above indexes were all statistically significant(all P<0.05).Conclusion Rhodojaponin Ⅲ may inhibit oxidative stress,inflammatory response,regulate bone metabolism and improve cartilage injury in post-traumatic osteoarthritis rats by activating Nrf2/HO-1 pathway.

rhodojaponin Ⅲpost-traumatic osteoarthritiscartilage injuryoxidative stressnuclear transcription factor E2-related factor/heme oxygen-1 pathway

刘举、苏彬、潘琦、崔振红、王希明

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济南市第四人民医院,创伤骨科,山东济南 250031

济南市第四人民医院,呼吸内科,山东济南 250031

闹羊花毒素Ⅲ 创伤后骨关节炎 软骨损伤 氧化应激 核转录因子E2相关因子/血红素加氧-1通路

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(7)
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