Objective:To study the pneumocystis carinii pneumonia(PCP) therapy effect of short interfering RNA targeting pneumocystis carinii major surface glycoprotein(MSG) gene’s upstream conserved sequence(UCS).Methods:Rat PCP model was established by hypodermic injection of dexamethasone twice a week for 8 weeks.20 rats with PCP were randomly divided into 4 groups:in plasmid PC MSG-UCS treatment group(pPC-UCS group)

rats were injected with short interfering plasmid PC MSG-UCS 500 μg/kg day for eight days;in plasmid TZU6+1 treatment group(pTZU6+1 group)

rats were injected with empty plasmid TZU6+1 500 μg/kg day for eight days;in sulfadiazine treatment group

rats were treated with compound sulfadiazine 120 mg/kg day for eight days;and in PCP control group

rats were not given any treatment.For each group

the rat survival rate

rat body weight

pathological changes in rat lung tissues

the number of PC cysts in rat lung tissues

the surface structure changes of PC under scanning electron microscopy

interleukin 8 and tumour necrosis factor alpha(TNF-α)in the serum of rats were tested.Results:All of the rats in each groups survived at the end of treatment.Rat survival rate had no significant difference in group comparsion.All of the rats in each group got weight during the course of treatment.The mean increased body weight of rats in pPC-UCS group

sulfadiazine treatment group

pTZU6+1 group and PCP control group were(13.16±3.97) g

(14.21±3.90) g

(5.38±1.19) g and(4.32±2.06) g

respectively.Those in pPC-UCS group and sulfadiazine treatment group were significantly higher than those in pTZU6+1 group and PCP control group.The inflammation of rat lung tissues in pPC-UCS group and sulfadiazine treatment group were less than those in pTZU6+1 group and PCP control group.Under light microscopy the mean cyst number per field in the rat lung tissues in pPC-UCS group and sulfadiazine treatment group were 3.61±0.4 and 3.17±0.28

respectively

significantly smaller than those in pTZU6+1 group

8.74±0.55

and PCP control group

8.34±0.57.Under scanning electron microscopy

PC in pTZU6+1 group and PCP control group had intact surface with dense microvillus structure;on the contrary

in pPC-UCS group and sulfadiazine treatment group

the PC surface showed no microvillus but deep gap.Interleukin 8 in rat serum of pPC-UCS group and sulfadiazine treatment group were(232.50±36.27) pg/ml and(201.15±34.52) pg/ml

respectively

significantly lower than those of pTZU6+1 group

(596.85±61.72) pg/ml and PCP control group

(555.10±54.31) pg/ml.TNF-α in rat serum of pPC-UCS group and sulfadiazine treatment group were(145.20±80.72) pg/ml and(172.65±76.27) pg/ml

respectively

significantly higher than those of pTZU6+1 group

(39.49±12.03) pg/ml and PCP control group

(31.58±8.47) pg/ml.Conclusion:Short interfering RNA targeting pneumocystis carinii major surface glycoprotein gene’s upstream conserved sequence is effective in the treatment of rat pneumocystis carinii pneumonia.