紫正地黄汤对颈深间隙感染大鼠炎性小体NLRP3的影响

目的:观察紫正地黄汤对颈深间隙感染大鼠炎性小体NLRP3的影响,探析紫正地黄汤治疗感染性疾病的作用机制。方法:取15月龄SD雄性大鼠60只,按随机数字表法分为空白组,模型组,对照组,紫正地黄汤低剂量组、中剂量组、高剂量组,每组10只。除空白组外,各组均参照毛氏方法制作颈深间隙感染模型,建模成功后连续用药5 d。观察大鼠一般情况及颈部感染灶的改变,分别用ELISA测定大鼠血清中IL-1β和IL-18水平,Western blot检测大鼠病灶局部组织的NLRP3及casepase-1蛋白的表达量,并观察病灶局部组织病理学变化。结果:造模后大鼠出现发热、精神不振、呼吸困难、局部红肿化脓,病灶局部组织NLRP3、casepase-1的表达及血清IL-1β和IL-18水平较空白组明显升高,差异均有统计学意义(P<0.05)。治疗5 d后,对照组和紫正地黄汤高、中、低剂量组大鼠的全身症状及局部红肿化脓等表现均明显改善,与模型组比较有统计学意义,并且各治疗组NLRP3、casepase-1、IL-1β和IL-18水平均明显低于模型组,差异均有统计学意义(P<0.01)。紫正地黄汤中剂量组大鼠NLRP3、casepase-1、IL-1β和IL-18水平与对照组比较无统计学意义(P> 0.05),而紫正地黄汤高剂量组对NLRP3及其下游炎性因子的调控明显优于对照组(P<0.05),紫正地黄汤低剂量组对NLRP3、casepase-1、IL-1β和IL-18的下调作用弱于对照组(P<0.05);紫正地黄汤高、中、低剂量组大鼠NLRP3、casepase-1、IL-1β和IL-18的表达呈递增趋势(P<0.05)。结论:紫正地黄汤对颈深间隙感染大鼠具有较好的治疗作用,其机制可能与其调控NLR径路实现抗炎作用有一定相关性。

Effects of Zizheng Dihuang Decoction on NLRP3 in Inflammatory Corpuscles of Rats with Deep Cervical Interstitial Infection

Objective:To observe the effects of Zizheng Dihuang Decoction on inflammatory corpuscle NLRP3 in rats with deep cervical interstitial infection and to explore the mechanism of the decoction in treating infectious diseases. Methods:According to random number table,a total of 60 SD male rats aged 15 months were divided into the blank group,model group,control group and the low,middle and high dosage groups of Zizheng Dihuang Decoction,with10 rats in each group. Except for the blank group,rat models with deep cervical interstitial infection were established with reference to the MAO’s method. After the model was established successfully,each group was continuously administered for 5 days. The changes of the lesions on the neck of rats were observed.Serum IL-1β and IL-18 levels were determined by ELISA,local tissue NLRP3 of the lesion in rats examined by Western blot and casepase-1 protein expression were detected,and the histopathological changes of the lesion were observed. Results:The model rats exhibited fever,lack of energy,difficulty in breathing,localized swelling and suppuration,the expression of NLRP3 and casepase-1 in the local tissue of the lesions and the levels of IL-1β and IL-18 in the serum were significantly higher than those in the blank group.There was statistically significant(P< 0.05). Compared with the model groups,after 5 days of treatment,the symptoms of the control group and the low,middle and high dosage groups of Zizheng Dihuang Decoction showed significant improvements in systemic symptoms and localized swelling and pus,and the levels of NLRP3,casepase-1 IL-1β and IL-18 were significantly lower than those in the model group,and the differences were statistically significant(P< 0.01). Compared with the control group,the levels of NLRP3,casepase-1,IL-1β and IL-18 in the middle dosage group had no statistically significant(P> 0.05),while the high dosage group had significantly better regulation of NLRP3 and its downstream inflammatory factors. The down-regulation of NLRP3,casepase-1,IL-1β,and IL-18 was weaker in the low dosage group than that in the control group(P< 0.05). The expressions of NLRP3,casepase-1,IL-1β and IL-18 in the high,middle,and low dosage groups increased gradually(P< 0.05). Conclusion:Zizheng Decoction has a good therapeutic effect on the rat model of deep cervical interstitial infection,the mechanism may be related to anti-inflammatory effect by regulating NLR pathway.