目的:探讨高钠盐与高脂肪喂养后大鼠血压、血脂变化、主动脉构型改变和辛伐他汀的干预作用及机制.方法:60只成年雄性SD大鼠,随机分为5组(n=12):对照组(N组)、高盐组(S组)、高脂组(F组)、高盐高脂组(SF组)和高盐高脂加辛伐他汀组(T组).喂养16周后,测量大鼠动脉压、血清甘油三酯(TG)、总胆固醇(TC)及可溶性CD40L(sCD40L)浓度;免疫组化法检测升主动脉根部血管壁组织CD40/CD40L表达;HE染色测量升主动脉起始段中膜层厚度和动脉内腔面积与血管腔横断面积比值.结果:(1) S组、F组和SF组收缩压与N组相比均明显增高(P<0.01),而T组与N组比增高但程度较SF组明显降低(P<0.05) ;(2)F组和SF组血清TG和TC明显升高,与N组和T组比较明显升高(P<0.001),而S组、N组和T组之间无明显差异;(3)S组、F组和SF组血清sCD40L浓度均高于N组和T组(P<0.05),SF组高于S组和F组(P<0.05),S组与F组、N组与T组间无明显差异;(4)S组、F组和SF组动脉组织CD40/CD40L表达强度高于N组和T组(P<0.05),且SF组高于S组和F组(P<0.05),S组与F组、N组、T组间无明显差异;(5)S组、F组与SF组动脉中膜厚度与N组比较明显增厚(P<0.01);T组与N组比无显著差异;S组、F组和SF组血管内腔面积/血管横断面积比(LA/TVA)与N组比较明显变小(P<0.05);T组与N组比较无显著差别.结论:高盐高脂喂养可导致大鼠血压升高和诱发动脉粥样硬化,以及血清sCD40L浓度升高、动脉组织CD40/CD40L表达强度增高;复合刺激改变明显强于单一因素作用.他汀类药物可通过抑制血清sCD40L及动脉组织CD40/CD40L表达途径保护血管.%AIM: To investigate the effect of simvastatin intervention on the changes of blood pressure, serum lipid fluctuation and aortic configuration induced by high - sodium and high - fat diet in rats. METHODS: Sixty adult male SD rats were randomly divided into 5 groups ( n = 12 ): control ( N )group, high salt ( S )group, high fat ( F ) group, high salt + high fat ( SF ) group and high salt + high fat + simvastatin ( T ) group. After fed for 16 weeks, the rats were subject to determine blood pressures and serum concentrations of triglycerides ( TG ), total cholesterol( TC ) and soluble CD40 ligand ( sCD40L ). The expression of CD40/CD40L in the root of ascending aorta was detected by immunohistochem-ical method. The thickness of intima media in the ascending aorta as well as the ratio of lumen area/total vascular area were measured and calculated after HE staining. RESULTS: In S group, F group and SF group, systolic blood pressure wassignificantly higher than that in N group ( P <0.01 ). Systolic blood pressure in T group were slightly higher than that in N group with statistical significance and significantly lower than that in SF group. The serum concentrations of TG and TC in F group and SF group were significantly higher than those in N group and T group ( P < 0. 01 ), and no significant difference among S group, N group and T group was observed. In S group, F group and SF group, the serum concentrations of sCD40L were higher than that in N group and T group ( P < 0.05 ), meanwhile that in SF group was also higher than that in S group and F group ( P <0.05 ). However, no significant difference of sCD40L concentration between S group and F group as well as N group and T group was observed. The expression of CD40/CD40L in the ascending aorta in S group, F group and SF group was higher than that in N group and T group ( P <0. 05 ), and that in SF group was also higher than that in S group and F group ( P <0. 05 ). No significant difference of CD40/CD40L expression between S group and F group as well as N group and T group was observed. The thickness of intima media in S group, F group and SF group was significantly thicker than that in N group ( P <0. 01 ), and no significant difference of the intima media thickness between T group and N group was observed. The ratio of lumen area/total vascular area in S group, F group and SF group was smaller than that in N group ( P <0. 05 ), and no significant difference of the ratio between T group and N group was found. CONCLUSION : Feeding high - fat and high - salt diet leads to blood pressure elevation, induces atherosclerosis, increases serum concentration of sCD40L and enhances the expression of CD40/CD40L in arterial tissues. The combination of the stimuli has stronger effect than a single factor. Statins protect the arterial tissues against atherosclerosis by decreasing the level of serum sCD40L and inhibiting the arterial expression of CD40/CD40L.
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