阿托伐他汀调节转化生长因子β与Smad通路对糖尿病脑梗死大鼠的影响

Effect of atorvastatin-regulated TGF-β/Smad signaling pathway in diabetic cerebral infarction rats

目的研究阿托伐他汀通过调节转化生长因子β(TGF-β)/Smad通路对糖尿病大鼠脑梗死的影响机制。方法60只雄性SD大鼠,根据随机数字表法选20只为假手术组(正常饲养),另40只随机分为模型组和阿托伐他汀组,给予高脂乳剂喂养2周后,尾静脉注射2%链脲佐菌素,建立糖尿病模型,再选造模成功大鼠用线栓法建立大脑中动脉缺血再灌注模型。假手术组和模型组给予等容积的生理盐水,阿托伐他汀组给予10 mg/kg阿托伐他汀。给药3 d后(第4天)用改良神经功能缺损评分(mNSS)评估3组大鼠神经损伤严重程度,造模成功后检测大鼠脑梗死体积、第2和4天糖脂代谢相关指标;用RT-PCR检测脑组织中TGF-β/Smad信号通路相关基因表达。结果模型组和阿托伐他汀组mNSS评分[(5.46±0.78)分和(3.14±0.45)分vs(0.63±0.13)分]和脑梗死体积[(415.46±80.68)mm^3和(243.13±54.43)mm^3vs(8.64±2.12)mm^3]均高于假手术组,且模型组高于阿托伐他汀组(P<0.05)。3组糖、脂代谢相关指标差异显著,其中模型组和阿托伐他汀组空腹胰岛素、胰岛素抵抗指数、糖化血红蛋白、TG、TC、LDL-C水平较假手术组显著增加,胰岛素敏感指数和HDL-C较假手术组显著降低,且阿托伐他汀组各项指标变化显著优于模型组,差异有统计学意义(P<0.05)。3组大鼠TGF-β/Smad信号通路相关基因表达水平差异显著,其中模型组、阿托伐他汀组TGF-β、Smad2、Smad4表达水平显著高于假手术组,而p21表达水平显著低于假手术组,且阿托伐他汀组各基因表达水平显著优于模型组,差异有统计学意义(P<0.05)。结论阿托伐他汀对脑缺血有保护作用,其作用机制可能与调节TGF-β/Smad信号通路有关。

Objective To study the effect of atorvastatin-regulated TGF-β/Smad signaling pathway in diabetic cerebral infarction(DCI)rats.Methods Sixty male SD rats were randomly divided into sham operation group,model group and atorvastatin treatment group(20 in each group).A DM model of rats was established by injecting 2%streptozotocin through the tail vein and a middle cerebral artery ischemia/reperfusion model of rats was stablished by Longa occlusion after they were fed on high fat emulsion for two weeks.The severity of nerve injury in 3 groups was assessed according to their mNSS score,the size of DCI was measured,the glycometabolism-related parameters and expressions of TGF-β/Smad signaling pathway-related genes in brain tissues of rats were detected on day 4 after the animals in sham operation group and model group were given an equivalent volume and those in atorvastatin treatment group were treated with atorvastatin(10 mg/kg).Results The mNSS score was significantly higher and the size of DCI was significantly larger in model group and atorvastatin treatment group than in sham operation group(5.46±0.78 and 3.14±0.45 vs 0.63±0.13,415.46±80.68 mm^3 vs 243.13±54.43 mm^3,P<0.05)and in model group than in atorvastatin treatment group(P<0.05).The expression levels of TGF-β,Smad2 and Smad4 were significantly higher while those of p21 were significantly lower in model group and atorvastatin treatment group than in sham operation group(P<0.05).The expression levels of different genes were significantly higher in atorvastatin treatment group than in model group(P<0.05).Conclusion Atorvastatin can protect brain against ischemia in rats by regulating the TGF-β/Smad signaling pathway.