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目的观察国产血管紧张素1型受体拮抗剂厄贝沙坦抑制兔颈动脉球囊损伤后再狭窄(RS)的作用,探讨 RS 可能的机理。方法将48只大耳白兔随机分为实验7、14、28 d 组并各设对照组(每组8只),以球囊损伤左颈总动脉,建立再狭窄模型。术后7、14、28 d 不同时点取材。实验组术前3 d 喂饲厄贝沙坦(35 mg/kg)至处死。病理 HE 染色观察动脉壁内、中膜面积、管腔面积;免疫组化法测定核因子-κB(NF-κB)、核增殖抗原(PCNA)核易位阳性细胞率;实时荧光定量聚合酶链反应(PCR)测定κB抑制蛋白(I-κB)、单核细胞趋化蛋白 mRNA 表达。结果厄贝沙坦实验组与对照组相比,术后7 d 时明显抑制内膜的增生(0.34 mm~2±0.15 mm~2 vs 1.05 mm~2±0.38 mm~2,P<0.05),28 d 时管腔面积明显较大(4.25 mm~2±0.29 mm~2 vs 2.56 mm~2±1.02 mm~2,P<0.05)。术后7 d 时厄贝沙坦明显抑制 NF-κB p65核易位(P<0.05)和 PCNA 的表达(P<0.05)。术后7 d 时厄贝沙坦实验组 I-κB mRNA 含量明显较低(7.2拷贝/μl±0.9拷贝/μl vs 15.6拷贝/μl±0.7拷贝/μl,P<0.05),厄贝沙坦实验组在各时相点均明显抑制 MCP-1 mRNA 的表达(P<0.05)。结论厄贝沙坦通过抑制NF-κB的激活而调控 MCP-1、PCNA 的表达,有效抑制再狭窄的发生发展。
Objective To observe the effect of irbesartan, a domestic angiotensin receptor type 1 receptor antagonist, on restenosis (RS) after balloon injury in rabbit carotid arteries and to explore the possible mechanism of RS. Methods 48 rabbits were randomly divided into 7, 14, 28 d groups and control group (8 in each group). The left common carotid artery was injured by balloon and the restenosis model was established. After 7,14,28 d at different time points drawn. The experimental group was given irbesartan (35 mg / kg) 3 days before operation to death. Pathological HE staining was used to observe the intramural, medial area and luminal area of the artery; immunohistochemistry was used to determine the nuclear translocation-positive rate of nuclear factor-κB (NF-κB) and nuclear proliferative antigen (PCNA); real-time fluorescence quantitative polymerase chain PCR was used to detect the expression of κB inhibitor (I-κB) and monocyte chemotactic protein (mRNA). Results Compared with the control group, the experimental group of irbesartan significantly inhibited the proliferation of the intima at 7 days (0.34 mm ± 2 ± 0.15 mm 2 vs 1.05 mm 2 ± 0.38 mm 2, P <0.05) At 28 days, the lumen area was significantly larger (4.25 mm ~ 2 ± 0.29 mm ~ 2 vs 2.56 mm ~ 2 ± 1.02 mm ~ 2, P <0.05). Irbesartan significantly inhibited nuclear translocation of NF-κB p65 (P <0.05) and PCNA expression (P <0.05) at 7 d after operation. The level of I-κB mRNA in irbesartan group was significantly lower at 7 days after operation (7.2 copies / μl ± 0.9 copies / μl vs 15.6 copies / μl ± 0.7 copies / μl, P <0.05) Group at each time point significantly inhibited the expression of MCP-1 mRNA (P <0.05). Conclusion Irbesartan regulates the expression of MCP-1 and PCNA by inhibiting the activation of NF-κB and effectively inhibits the development of restenosis.