氧化苦参碱对糖尿病视网膜病变大鼠视网膜Toll样受体4 mRNA和核转录因子κB mRNA表达的影响

Effect of oxymatrine on the expression of Toll like receptor 4 mRNA and nuclear factor κB mRNA in retina of diabetic retinopathy rats

目的观察氧化苦参碱对糖尿病视网膜病变(DR)大鼠视网膜Toll样受体4(TLR4)mRNA及核转录因子κB(NF-κB)mRNA表达水平的影响。方法将60只雄性SD大鼠按照随机数字表法分为空白组、模型组、对照组及氧化苦参碱低、中、高剂量组6组,每组10只。空白组大鼠常规饲养,其余组大鼠予50 mg/kg的链脲佐菌素(STZ)快速腹腔注射制作糖尿病大鼠模型。造模成功后,对照组大鼠予羟苯磺酸钙150 mg/(kg·d)灌胃;氧化苦参碱低、中、高剂量组大鼠分别予氧化苦参碱50、100、150 mg/(kg·d)灌胃;空白组、模型组予等容积蒸馏水灌胃。连续给药12周后,取大鼠视网膜组织,采用逆转录聚合酶链式反应(RT-PCR)测定大鼠视网膜TLR4 mRNA、NF-κB mRNA的表达。结果模型组、对照组及氧化苦参碱低、中剂量组大鼠视网膜TLR4 mRNA相对表达量高于空白组(P<0.05);模型组、对照组及氧化苦参碱低、中、高剂量组大鼠视网膜NF-κB mRNA相对表达量高于空白组(P<0.05)。对照组及氧化苦参碱低、中、高剂量组大鼠视网膜TLR4 mRNA、NF-κB mRNA相对表达量均低于模型组(P<0.05)。氧化苦参碱低剂量组大鼠视网膜TLR4 mRNA、NF-κB mRNA相对表达量与对照组比较差异无统计学意义(P>0.05);氧化苦参碱中、高剂量组大鼠视网膜TLR4 mRNA、NF-κB mRNA相对表达量均低于对照组及氧化苦参碱低剂量组(P<0.05);氧化苦参碱高剂量组大鼠视网膜TLR4 mRNA、NF-κB mRNA相对表达量低于氧化苦参碱中剂量组(P<0.05)。结论氧化苦参碱可通过抑制DR大鼠视网膜TLR4mRNA、NF-κBmRNA的表达,改善DR大鼠视网膜病变情况。

Objective To observe the effects of oxymatrine on the expression of Toll like receptor 4(TLR4)mRNA and nuclear factorκB(NF-κB) mRNA in retina of diabetic retinopathy(DR) rats. Methods 60 male SD rats were randomly divided into blank group, model group, control group and low, medium and high dose oxymatrine group, with 10 rats in each group. The rats in blank group were fed routinely, while rats in other groups were injected 50 mg/kg of streptozotocin(STZ) into abdominal cavity to make diabetic rat model. After successful establishment of the model, rats in the control group were subcutaneously injected with calcium hydroxybenzene carbonate for 150 mg/(kg·d)by gavage;rats in the low, medium and high dose groups were given oxymatrine 50, 100 and 150 mg/(kg·d) by gavage respectively;rats in the blank group and the model group were given equal volume distilled water by gavage. After 12 weeks of continuous administration, the rat retinal tissue was taken and the expression of TLR4 mRNA and NF-κB mRNA in rat retina was determined by reverse transcription polymerase chain reaction(RT-PCR). Results The relative expression of TLR4 mRNA in retina of rats in model group, control group and low dose and medium dose oxymatrine groups was higher than that in blank group(P<0.05). The relative expression of NF-κB mRNA in retina of rats in model group, control group and low dose, medium dose and high dose oxymatrine groups was higher than that in blank group(P<0.05). The relative expression of TLR4 mRNA and NF-κB mRNA in retina of rats in control group and oxymatrine low, medium and high dose groups were lower than those in model group(P<0.05). There was no significant difference in the relative expression of TLR4 mRNA and NF-κB mRNA in retina of rats between the low dose oxymatrine group and the control group(P>0.05). The relative expressions of TLR4 mRNA and NF-κB mRNA in retina of rats in medium and high dose oxymatrine group were lower than those in control group and low dose oxymatrine group(P<0.05). The relative expression of TLR4 mRNA and NF-κB mRNA in retina of rats in high dose oxymatrine group was lower than that in medium dose oxymatrine group(P<0.05). Conclusion Oxymatrine can improve the retinopathy of DR rats by inhibiting the expression of TLR4 mRNA and NF-κB mRNA in the retina of DR rats.