Mechanism of Guiqi Yiyuan Ointment in regulating the lung and kidney injury of 12C6+beam radiation-bystander effect in rats through NLRP3/ASC/caspase-1 pathway
Objective:To observe the effects of Guiqi Yiyuan Ointment on lung and kidney injury in rats with radiation-bystander effect,and to explore its mechanism through NLRP3/ASC/caspase-1 pathway mediated by reactive oxygen species(ROS).Methods:Seventy Wistar rats were randomly divided into blank group,model group,inhibitor group,Western medicine group and Chinese medicine high,middle and low dose group,with 10 rats in each group.Before irradiation,the high,middle and low doses of Chinese medicine were gavaged Guiqi Yiyuan Ointment as follows:4.8,2.4,1.2 g/kg,respectively for 14 days.In the inhibitor group,ROS inhibitor acetylcysteine was intraperitoneally injected for 7 days(40 mg/200 g).The western medicine group was given a single intrabitoneal injection of amifotene(28 mg/200 g)30 min before radiation,and the blank and model groups were given equal volume of normal saline.On the 15th day,except the blank group,the right lung of rats in each group was irradiated by a single beam of 4 Gy 12C6+.After 3 d,the serum and kidney tissues were collected,and pathological changes were detected by HE staining,ROS expression was detected by immunofluorescence,the contents of ROS,IL-1β,IL-18 and TNF-α in serum were measured by ELISA,and the levels of BUN and Cr in serum were detected.The mRNA expression of NLRP3,ASC,caspase-1 and NF-κB p65 in renal tissue were detected by PCR,and the protein expression of NLRP3,ASC,caspase-1 and p-NF-κB p65/NF-κB p65 were detected by Western Blot.Results:Compared with blank group,ROS levels in renal tissue of model group were increased(P＜0.05).Serum ROS,IL-1β,IL-18,TNF-α,BUN and Cr levels were increased(P＜0.05).The mRNA and protein expressions of NLRP3,ASC,caspase-1 and p-NF-κB p65/NF-κB p65 in renal tissues were increased(P＜0.05).Compared with model group,ROS level in kidney of rats in each administration group was decreased(P＜0.05).Serum ROS,IL-1β,IL-18 and TNF-α contents were decreased(P＜0.05).BUN and Cr levels were decreased;The mRNA and protein expressions of NLRP3,ASC,caspase-1,p-NF-κB p65/NF-κB p65 in kidney were decreased to varying degrees.Conclusion:Guiqi Yiyuan Ointment can effectively reduce the damage caused by radiation and paraprenal effect,and its mechanism may be related to the activation of NLRP3 inflammasome mediated by ROS.
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