ABSTRACT
BACKGROUND: The mortality of patients infected with hepatic alveolar echinococcosis (HAE) was higher. The aim of this study was to investigate the therapeutic effect of nanosecond pulsed electric fields (nsPEFs) on HAE in rats and explore the related molecular mechanisms. METHODS: Establishment of HAE rat model and the lesions were treated with nsPEFs. The RNA of lesions in the high voltage nsPEFs treatment group and model group were extracted, and lncRNA and mRNA sequence analyses was performed. After obtaining the differentially expressed lncRNAs and mRNAs between the two groups, enrichment analysis was performed for mRNAs. The target genes of lncRNAs were predicted through co-location and co-expression. The expression of important lncRNAs and target genes in lesions was detected by qPCR. RESULTS: The HAE rat model was successfully established. After nsPEFs treatment, the size of lesions was improved significantly. Then, we identified 270 differentially expressed lncRNAs and 1659 differentially expressed mRNAs between the high voltage nsPEFs treatment group and model group. Enrichment analysis showed that the differentially expressed mRNAs were mainly enriched in metabolism and inflammation. Five important lncRNAs regulatory networks were identified, then Cpa1, Cpb1, Cel, Cela2a, and Cela3b were identified as key target genes. Importantly, the expression of 5 lncRNAs and 5 target genes was verified in the lesions. CONCLUSIONS: Preliminary results had shown that HAE treatment with nsPEFs can inhibit the growth of lesions. NsPEFs treatment altered gene expression in the lesions, and some genes were regulated by lncRNAs. The therapeutic mechanism may involve metabolism and inflammation.
Subject(s)
Echinococcosis, Hepatic , RNA, Long Noncoding , Rats , Animals , Gene Regulatory Networks , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Echinococcosis, Hepatic/therapy , RNA, Messenger/genetics , RNA, Messenger/metabolism , Inflammation , Gene Expression ProfilingABSTRACT
Objective:To investigate the changes of natural killer (NK) cells, natural killer T (NKT) cells and T lymphocytes in the peripheral blood after nanosecond pulse ablation of hepatic vesicular hydatid in rats with different energy levels.Methods:A total of 32 SD rats were randomly divided into hepatic vesicular hydatid model group, low voltage group (1 000 V), medium voltage group (1 500 V) and high voltage group (2 000 V). The hydatid model of rats was established by selective injection of 100 μl of echinococcosis head suspension with concentration of 500/100 μl into the left hepatic portal vein in all the 4 groups. After 3 months, nanosecond pulse therapy was applied to the left lobe vesicular hydatid lesions in the low voltage group, medium voltage group and high voltage group. On the third day after treatment, flow detector was used to calculate the ratio of CD 4+ T to CD 8+ T in peripheral blood of four groups by CD 3+ T, CD 4+ T, CD 8+ T, NK cells and NKT cells. Results:CD 3+ T was expressed in the high voltage group with (62.08±2.75)%, the medium voltage group with (63.84±7.73)%, the low voltage group with (55.19±8.55)% and the control group with (54.76±8.28)% ( P<0.05). CD 4+ T number was larger in high voltage group (43.7±6.51)% than medium voltage group (38.82±5.47)%, low voltage group (37.31±6.96)% and model group (38.12±3.04)% ( P<0.05). CD 8+ T ratio in the high voltage group was (20.03±2.40)%, the medium voltage group was (21.22±1.74)%, the low voltage group was (19.00±3.06)%, and the model group (20.56±3.98)%, with no statistically significant difference ( P>0.05). NK cells ratio in high voltage group was (6.49±1.60)%, medium voltage group was (3.02±0.32)%, low voltage group was (3.42±0.91)% and model group was (3.44±0.55)% ( P<0.05). NKT cells ratio in high voltage group was (1.53±0.16)%, medium voltage group was (0.82±0.09)%, in low voltage group was (0.70±0.17)% and model group (0.78±0.10)% ( P<0.05). CD 4+ T/CD 8+ T high voltage group was (2.26±0.65), medium voltage group was (1.90±0.40), low voltage group was (1.98±0.37) and model group was (2.06±0.35) ( P<0.05). Conclusion:High voltage (2 000 V) increased number of T, NK and NKT cells in peripheral blood compared with medium voltage (1 500 V) and low voltage (1 000 V), which may be the immune response of the body caused by nanosecond pulse ablation of hepatic vesicular hydatid in rats.
