Objective To observe the effect of electroacupuncture(EA)on the rhythm of running-wheel activity of hepatocellular carcinoma(HCC)mice and the expression of Per 1 and Per 2(circadian rhythm genes)in the hypothalamic suprachiasmatic nucleus(SCN)

so as to investigate its mechanism underlying regulating circadian rhythm.Methods A total of 108 male C 57 BL/6 Jmice were randomly divided into control

HCC model and EA groups which were further assigned to six zeitbeger(environmental light-dark cycle)time(ZT)point(ZT 0

ZT 4

ZT 8

ZT 12

ZT 16 and ZT 20)subgroups.The HCC model was established by injection of H 22 cancer cell(abdominal 3 rd generation

10!L)suspension into the larger live lobe.Mice of the control group received saline injection of the liver lobe.EA(2 Hz/15 Hz

0.2 mA)was applied to bilateral"Ganshu"(BL 18)and"Zhiyang"(GV 9)for 15 min

once daily for 10 days.Mice of the control and model groups received the same binding-fixing to those of the EA group.Circadian running-wheel activity of 12 h∶12 hlight darkness(LD)cycle(activity onset and acrophase of actogram

amplitude or peak of periodogram)was recorded by using ClockLab(ACT-500)software and analyzed by MATLAB(R2007 b)before and after EA treatment.The pathological changes of liver cells were observed under light microscope after sectioning and H.E.staining.The expression levels of Per 1 mRNA and Per 2 mRNA in the liver tissues were determined by fluorogenic quantitative real time-PCR.Results(1)Following modeling

the amplitude of periodogram of running-wheel activity was significantly lowered at ZT 0

ZT 4

ZT 8

ZT 12

ZT 16

and ZT 20 relevant to the control group(P<0.05).After EA intervention

the amplitude of periodogram at ZT 8(15:00)was considerably increased relevant to the model group(P<0.05)

and the acrophase at ZT 8 was remarkably advanced(P<0.05).No significant changes were found in the onset time and periods of periodogram at the 6 time-points after modeling and EA intervention(P>0.05).(2)The expression levels of Per 1 mRNA and Per 2 mRNA in the SCN were significantly up-regulated at the 6 time-points in the model group relevant to the control group(P<0.05)

and obviously down-regulated at ZT 8 after EA intervention relevant to the model group(P<0.05).Conclusion EA can benignly regulate the rhythm of running-wheel activity of HCC mice

which may be closely related to its effect in down-regulating the expression of circadian rhythm genes Per 1 and Per 2 in the SCN.