血管紧张素Ⅱ1型受体自身抗体阳性雌鼠孕后出现妊娠期高血压样症状
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摘要
目的探究血管紧张素Ⅱ1型受体自身抗体(angiotensinⅡtype 1 receptor autoantibody,AT1-AA)阳性大鼠孕后是否出现类妊娠期高血压疾病的表现。方法收集临床血清样品,通过酶联免疫吸附实验(enzyme linked immunosorbent assay,ELISA)检测非妊娠的健康女性体内是否含有AT1-AA。通过主动免疫方法建立AT1-AA阳性大鼠模型,利用尾套法测量大鼠收缩压,肠系膜动脉血管环检测血管功能。结果 8. 3%未妊娠的健康女性体内含有AT1-AA。AT1-AA阳性大鼠怀孕前与对照组大鼠的血压比较,差异无统计学意义(P>0. 05);但怀孕后AT1-AA阳性大鼠的收缩压较对照组孕鼠显著升高。肠系膜动脉血管环实验结果显示,AT1-AA阳性大鼠怀孕后血管对收缩物质的反应性增强(对照组:110%±5%,模型组:130%±10%,P <0. 05),且内皮依赖/非依赖血管舒张功能降低(对照组:90%±4%,模型组:60%±7%/对照组:95%±1%,模型组:75%±3%,P <0. 05)。结论AT1-AA阳性大鼠妊娠期间出现血压升高,阻力血管功能受损等类妊娠期高血压的病理表现,提示健康人体内存在的AT1-AA是妊娠期高血压疾病发生的潜在危险因素。
Objective To investigate whether angiotensin Ⅱ type 1 receptor autoantibody( AT1-AA)-positive rats exhibited the phenomenon of gestational hypertension after pregnancy. Methods Clinical serum samples were collected to detect the presence of AT1-AA in non-pregnant healthy women by enzyme linked immunosorbent assay( ELISA). AT1-AA-positive rat model was established by active immunization. Tail-cuff method was used to measure the systolic blood pressure and the mesenteric artery ring was used to detect vascular function. Results AT1-AA was also present in some healthy women who were not pregnant. There was no significant difference in blood pressure between AT1-AA-positive rats and control rats before pregnancy,but the systolic pressure of AT1-AA-positive rats after pregnancy was significantly higher than that of control rats. Mesenteric artery ring showed that the vasoconstriction was increased( vehicle group: 110% ± 5%,immunized group: 130% ± 10%,P < 0. 05),and endothelium-dependent/non-endothelium-dependent vasodilation was decreased in AT1-AA-positive rats after pregnancy( vehicle group: 90% ± 4%,immunized group: 60% ± 7%/vehicle group: 95%± 1%,immunized group: 75% ± 3%,P < 0. 05). Conclusion AT1-AA-positive rats after pregnancy showed the phenomenon of gestational hypertension,such as elevated blood pressure and impaired vascular function. These suggested that the presence of AT1-AA in healthy individuals was a risk factor for gestational hypertension.
Objective To investigate whether angiotensin Ⅱ type 1 receptor autoantibody( AT1-AA)-positive rats exhibited the phenomenon of gestational hypertension after pregnancy. Methods Clinical serum samples were collected to detect the presence of AT1-AA in non-pregnant healthy women by enzyme linked immunosorbent assay( ELISA). AT1-AA-positive rat model was established by active immunization. Tail-cuff method was used to measure the systolic blood pressure and the mesenteric artery ring was used to detect vascular function. Results AT1-AA was also present in some healthy women who were not pregnant. There was no significant difference in blood pressure between AT1-AA-positive rats and control rats before pregnancy,but the systolic pressure of AT1-AA-positive rats after pregnancy was significantly higher than that of control rats. Mesenteric artery ring showed that the vasoconstriction was increased( vehicle group: 110% ± 5%,immunized group: 130% ± 10%,P < 0. 05),and endothelium-dependent/non-endothelium-dependent vasodilation was decreased in AT1-AA-positive rats after pregnancy( vehicle group: 90% ± 4%,immunized group: 60% ± 7%/vehicle group: 95%± 1%,immunized group: 75% ± 3%,P < 0. 05). Conclusion AT1-AA-positive rats after pregnancy showed the phenomenon of gestational hypertension,such as elevated blood pressure and impaired vascular function. These suggested that the presence of AT1-AA in healthy individuals was a risk factor for gestational hypertension.
引文
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[12] Parrish M R,Murphy S R,Rutland S,et al. The effect of immune factors,tumor necrosis factor-alpha,and agonistic autoantibodies to the angiotensinⅡtype I receptor on soluble fms-like tyrosine-1 and soluble endoglin production in response to hypertension during pregnancy[J]. Am J Hypertens,2010,23(8):911-916.
[13] Harmon A C,Cornelius D C,Amaral L M,et al. The role of inflammation in the pathology of preeclampsia[J]. Clin Sci(Lond),2016,130(6):409-419.
[14]张真真,戴姝艳.血管紧张素Ⅱ2型受体对大鼠子宫内膜异位症血管生成的影响[J].中国医科大学学报,2018,47(9):792-796.
[2] Cunningham M W,Castillo J,Ibrahim T,et al. AT1-AA(angiotensinⅡtype 1 receptor agonistic autoantibody)blockade prevents preeclamptic symptoms in placental ischemic rats[J]. Hypertension,2018,71(5):886-893.
[3] Wallukat G,Homuth V,Fischer T,et al. Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor[J]. J Clin Invest,1999,103(7):945-952.
[4] Lei J,Li Y,Zhang S,et al. The prognostic role of angiotensinⅡtype 1 receptor autoantibody in non-gravid hypertension and pre-eclampsia:a meta-analysis and our studies[J]. Medicine(Baltimore),2016,95(17):e3494.
[5] Zhou C C,Zhang Y,Irani R A,et al. Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice[J]. Nat Med,2008,14(8):855-862.
[6] Yang J,Li L,Shang J Y,et al. AngiotensinⅡtype 1 receptor autoantibody as a novel regulator of aldosterone independent of preeclampsia[J]. J Hypertension,2015,33(5):1046-1056.
[7] La Marca B,Wallace K,Granger J. Role of angiotensinⅡtype I receptor agonistic autoantibodies(AT1-AA)in preeclampsia[J]. Curr Opin Pharmacol,2011,11(2):175-179.
[8] Cunningham M W,Williams J M,Amaral L,et al. Agonistic autoantibodies to the angiotensinⅡtype 1 receptor enhance angiotensinⅡ–induced renal vascular sensitivity and reduce renal function during pregnancy[J]. Hypertension,2016,68(5):1308-1313.
[9] Zhang S,Zheng R,Yang L,et al. Angiotensin type 1 receptor autoantibody from preeclamptic patients induces human fetoplacental vasoconstriction[J]. J Cell Physiol,2013,228(1):142-148.
[10] Yang X,Wang F,Chang H,et al. Autoantibody against AT1 receptor from preeclamptic patients induces vasoconstriction through angiotensin receptor activation[J]. J Hypertens,2008,26(8):1629-1635.
[11] Wang B,Liao Y,Zhou Z,et al. Arterial structural changes in rats immunized by AT1-receptor peptide[J]. Heart Vessels,2005,20(4):153-158.
[12] Parrish M R,Murphy S R,Rutland S,et al. The effect of immune factors,tumor necrosis factor-alpha,and agonistic autoantibodies to the angiotensinⅡtype I receptor on soluble fms-like tyrosine-1 and soluble endoglin production in response to hypertension during pregnancy[J]. Am J Hypertens,2010,23(8):911-916.
[13] Harmon A C,Cornelius D C,Amaral L M,et al. The role of inflammation in the pathology of preeclampsia[J]. Clin Sci(Lond),2016,130(6):409-419.
[14]张真真,戴姝艳.血管紧张素Ⅱ2型受体对大鼠子宫内膜异位症血管生成的影响[J].中国医科大学学报,2018,47(9):792-796.