Abstract: Objective To explore the influence of short interfering hybrids(Sihybrids) on the expression level of kpc-2 gene and the antibacterial effects of meropenem in carbapenem-resistant Klebsiella pneumoniae(CRKP) and study the action mechanism of sihybrids. Methods Total 48 strains carrying kpc-2 gene resistant to carbapenems Klebsiella Klebsiella strains cultured per plant were divided into three copies,one without siHybrids as control group,two other join siHybrids as experimental group.The experimental group was divided into low concentration group(siHybrids interference dose for 0.125 μg/ml and high concentration group(siHybrids interfere with dose of 8.0 μg/ml).RT-PCR was performed in the three groups to detect the expression of the mRNA of kpc-2 gene in bacterial fluid taken at 12 h,24 h,and 48 h time points.The amount of mRNA at three time points were calculated and compared among the three groups to determine the effect of siHybrids on the expression level of kpc-2 gene.The meropenem susceptibility tests were performed to observe the antibacterial circle diameter and infer indirectly the effects of siHybrids on the expression yield of kpc-2. Results Compared with the control group,the mRNA expression of kpc-2 gene was significantly decreased after the intervention of siHybrids(P<0.05).The mRNA expression of kpc-2 gene in high concentration group was significantly lower than that in low concentration group(P<0.05);the concentration of siHybrids was negatively correlated with the mRNA expression of kpc-2 gene(r=-0.782,P=0.014);the mRNA expression of kpc-2 gene decreased significantly(P<0.05) with the prolongation of siHybrids intervention time.SiHybrids intervention can significantly increase the diameter of inhibition zone of meropenem(P<0.05),different concentrations of siHybrids of meropenem antibacterial circle diameter increased dramatically different,group of high concentration of meropenem antibacterial circle diameter was significantly greater than that of the low concentration group(P<0.05).The concentration of meropenem and the diameter of inhibition zone was positively related to the size of siHybrids(r=0.882,P=0.024). conclusion Sihybrids can reduce kpc-2 gene expression level in carbapenem-resistant Klebsiella pneumonia,improve the antibacterial effect of meropenem,and its mechanism of action may be specific silencing of the Klebsiella pneumoniae kpc-2 gene by siHybrids molecule.