二氧化硫对自发性高血压大鼠血管胶原重构的影响

Effect of sulfur dioxide on vascular collagen remodeling in spontaneously hypertensive rats

目的研究自发性高血压大鼠（spontaneously hypertensive rat，SHR）血管重构时二氧化硫（SO2）对Ⅰ、Ⅲ型胶原蛋白在主动脉管壁异常堆积的调节作用，进一步探讨SO2缓解SHR血管重构的作用机制。方法4周龄雄性WistarKyoto（WKY）大鼠8只，同样周龄雄性SHR16只随机分为SHR对照组（n=8）、SHR＋Na2S03／NaHS03（S02供体）组（n=8）。5周后测定大鼠血压，胸主动脉显微结构，血浆SO2含量以及主动脉Ⅰ、Ⅲ型胶原蛋白的表达。结果（1）与WKY大鼠相比，SHR的血压升高53％，左室与全心重量比增加6％，血浆SO，含量下降44％（P〈0．01，P〈0．05）；与SHR组相比，SHR＋Na2SO3／NaHSO3组血压降低26％，血浆SO2含量升高28％（P均〈0．01）。（2）各组大鼠胸主动脉壁厚与内径之比：SHR组较WKY大鼠增加28％（P〈0．01），SHR＋Na2SO3／NaHSO3组较SHR组减少10％（P〈0．01）。（3）各组大鼠胸主动脉中Ⅰ型胶原蛋白的表达：SHR较WKY大鼠增加10％（P〈0．01）；SHR＋Na2S03／NaHS03组较SHR组减少5％（P〈0．01）。（4）各组大鼠胸主动脉中Ⅲ型胶原蛋白的表达：SHR组较WKY组增加13％（P〈0．01）；SHR＋Na2SO3／NaHSO3组较SHR组减少8％（P〈0．01）。结论SO2能够抑制Ⅰ、Ⅲ型胶原蛋白在血管壁的表达，可能是其缓解高血压血管重构的作用机制之一。

Objective To study the modulatory effect of sulfur dioxide （SO2 ）on the accumulation of collagen type Ⅰ and type Ⅲ in the wall of aorta during spontaneously hypertensive rat （SHR） vascular remodeling. Methods Eight male Wistar Kyoto rats at the age of 4 weeks with normal blood pressure were used as a control group. And sixteen male SHRs at the age of 4 weeks were randomly divided into an SHR control group and SHR ＋ Na2SO3/NaHSO3 （SO2 donor）group. Na2SO3/NaHSO3 solution was injected intraperitoneally everyday to the rats in the SHR ＋ Na2SO3/NaHSO3 group. After 5 weeks, the systemic blood pressure was measured. The weight ratio of left ventricle to the whole heart was also measured. The rat aorta was dyed with Hart＇s method. The morphometric parameters including outer radius, lumen radius and the wall thickness were calculated by Leica workstation. The plasma level of SO2 was determined by HPLC method. The expressions of collagen type Ⅰ and type Ⅲ in aorta were detected by immunohistochemistry. Results （ 1 ） Compared with the WKY rat control group, the systolic blood pressure increased by 53 %, the weight ratio of left ventricle to the whole heart increased by 6% but the plasma level of SO2 decreased by 44% for rats in the SHR group （P 〈 0. 01 or P 〈 0. 05 ）. Compared with the SHR control group, the systolic blood pressure decreased by 26% , but the plasma level of SO2 increased by 28% （ all P 〈 0. 01 ）for rats in the SHR ＋ Na2SO3/NaHSO3 group. （2）Compared with the WKY rats, the ratio of media to lumen radius increased by 28% for SHR. Compared with the SHR group, the ratio of media to lumen radius decreased by 10% （P 〈 0. 01 ） in rats of the SHR ＋ Na2 SO3/NaHSO3 group. （3） Compared with rats in the WKY control group, collagen type I expression increased by 10% for rats in the SHR group（P 〈 0. 01 ）.Compared with the SHR group, however, the expression decreased by 58% for rats in the SHR ＋ Na2SO3/ NaHSO3 group（ P 〈 0.01 ）. （4）Compared with rats in the WKY control group, the expression increased by 13% for rats in the hypoxia SHR group（P 〈 0. 01 ） ;however, compared with rats in the SHR group, the expression decreased by 8% in the rats of the SHR ＋ Na2SO3/NaHSO3 group（P 〈 0.01 ）. Conclusions In the process of SHR vascular collagen remodeling in the rats, SO2 could inhibit the abnormal accumulation of collagen type Ⅰ and type Ⅲ in the wall of aorta. This effect may be one of the mechanisms by which SO2 ameliorates SHR vascular remodeling.