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【目的】观察清热解毒法对肺炎衣原体(Cpn)感染致动脉粥样硬化(AS)发病进程的干预作用。【方法】在轻度高脂饲料(含2．5g/kg胆固醇)喂养条件下,以Cpn经鼻腔接种52只新西兰兔,6周内共3次接种,6周末抽血检测Cpn特异性IgG抗体(Cpn-IgG),阳性者(N=44)随机分为4组:中药高剂量组(A组)、中药低剂量组(B组)、西药组(C组)和模型对照组(D组),每组11只,分别以高剂量黄连解毒汤(HJD)(2g·kg-1·d-1)、低剂量HJD(1 g·kg-1·d-1)、阿奇霉素 (20mg·kg-1·d-1)和生理盐水灌胃6周,另设立高脂对照组(E组,N=8)。接种前、接种后、治疗后分别采血检测血清高敏C反应蛋白(hs-CRP)的水平,治疗后再次检测Cpn-IgG,第18周末处死全部动物取主动脉标本进行病理学观察,并分别采用聚合酶链反应(PCR)和免疫组化法检测该组织中Cpn-DNA、肿瘤坏死因子α(TNF-α)的表达。【结果】实验结束时,在D组和E组模型兔主动脉上均观察到典型的AS病理改变,前者更为严重。与D组相比,A、C两组模型兔的主动脉 AS病理损害明显减轻,AS指数如最大内膜厚度、AS病变占管周百分比、斑块面积指数等明显改善(均P<0．05或P< 0．01),B组也有一定程度的改善但不及前两组明显;各组主动脉标本Cpn-DNA检测均为阴性;动脉壁TNF-α的表达与AS的病变严重程度明显相关,其表达集中于AS病灶区;第12周末C组血清Cpn-IgG阳性率明显低于A、B、D组,差异均有显著性意义,而后3组间差异无显著性意义;C组接种Cpn后血清hs-CRP水平较E组明显升高,差异有非常显著性意义,治疗后 C组和D组比较无显著性差异,而A、B组hs-CRP水平明显降低,与D组比较差异有显著性意义(均P<0．05或P<0．01)。【结论】Cpn感染可复制AS兔模型,hs-CRP、TNF-α等炎症因子激活参与了AS的发病。阿奇霉素和HJD均能抑制这种AS的病理进程,阿奇霉素可能主要通过抗Cpn感染发挥作用,而HJD可能通过拮抗Cpn感染引发的炎症过度反应而发挥作用。
【Objective】 To observe the intervention of Qingrejiedu on the pathogenesis of atherosclerosis (AS) caused by Chlamydia pneumoniae (Cpn) infection. 【Methods】 Fifty-two New Zealand rabbits were inoculated intranasally with Cpn under mild high-fat diet (containing 2.5g/kg cholesterol), three times inoculation within 6 weeks, and blood was drawn at 6 weeks to detect Cpn-specific IgG antibody. (Cpn-IgG), positive (N=44) were randomly divided into 4 groups: high dose group (group A), low dose group (group B), western medicine group (group C) and model control group (group D) ), 11 in each group, with high-dose Huanglianjiedu Decoction (HJD) (2g·kg-1·d-1), low-dose HJD (1g·kg-1·d-1), and azithromycin (20mg·kg) -1·d-1) and normal saline were given for 6 weeks, and a high-fat control group (E group, N=8) was established. Serum levels of high-sensitivity C-reactive protein (hs-CRP) were measured before, after, and after inoculation, Cpn-IgG was detected again after treatment, and all animals were sacrificed at the end of the 18th week for pathological observation of aortic specimens. Polymerase chain reaction (PCR) and immunohistochemistry were used to detect the expression of Cpn-DNA and tumor necrosis factor-α (TNF-α). 【Results】 At the end of the experiment, typical pathological changes of AS were observed in the aorta of the D and E groups. The former was more severe. Compared with group D, pathological lesions of aorta AS were significantly reduced in groups A and C, and AS indexes such as maximum intimal thickness, percentage of AS lesions in the peritubular area, and patch area index were significantly improved (all P<0. 05 or P< 0.01), group B also improved to a certain extent but less than the first two groups; all groups of aortic specimens were negative for Cpn-DNA; arterial wall TNF-α expression and AS lesions were significantly Correlation, its expression was concentrated in the lesion area of AS; at the 12th weekend, the positive rate of serum Cpn-IgG in group C was significantly lower than that of group A, B, and D, and the difference was significant. There was no significant difference between the latter three groups; The serum hs-CRP level after Cpn vaccination was significantly higher than that of E group, and the difference was significant. After treatment, there was no significant difference between C and D groups, but the level of hs-CRP in groups A and B was significantly lower, compared with D group. The difference was significant (all P<0.05 or P<0.01). 【Conclusion】 Cpn infection can replicate the AS rabbit model, and the activation of inflammatory factors such as hs-CRP and TNF-α is involved in the pathogenesis of AS. Azithromycin and HJD can inhibit the pathological process of this AS, azithromycin may play a role mainly through the anti-Cpn infection, and HJD may play a role by antagonizing the inflammatory over-reaction caused by Cpn infection.