The Effect Of Hepatic Denervation On Liver Regeneration After Partially Hepatectomy In Rats

Objective: To investigate the effects of hepatic sympathetic denervation, hepatic vagotomy and total hepatic denervation on liver regeneration after partially hepatectomy in rats, and to explore the roles and mechanism of hepatic nerve in liver regeneration.Methods: Male SD rats (n=186)were randomly divided into 4 groups: partially hepatectomy(PH), partially hepatectomy after hepatic sympathetic denervation (PHS), partially hepatectomy after hepatic vagotomy(PHV) and partially hepatectomy after total hepatic denervation(PHT) groups. Rats in each group were killed at 12, 24, 36, 48, 72, 120 and 168 h after operation respectively. The liver to body weight ratio were measured at each time point, and silver staining method and Elisa methods were used to detect argyrophilic nucleolar organizer region associated proteins (AgNORs) and serum estrogen levels respectively. Immunohistochemistry method was used to detect hepatocytes PCNA and MMP-9 expression respectively at each time point.Results: (1) The liver to body weight ratio: Compared with PH group , the liver to body weight ratio of PHS group rats increased significantly at 48 h and 168 h after operation(P<0.05), PHV group rats decreased significantly at 168 h after operation(P<0.05), and PHT group rats increased at 48 h-120 h after operation, but the liver to body weight ratio of PHT group rats increased significantly at 168 h after operation(P<0.05). (2) AgNORs: Compared with PH group , the average number of AgNORs particles in PHS group rats was significantly lower at 24h-48h and 120h after operation (P<0.05), and peak value was delayed, and average diameter of AgNORs particle of regeneration hepatocytes was increased , and increased significantly at 168 h after operation(P<0.05); The average number of AgNORs particles in PHV group rats was significantly increased at 24h-48h after operation (P<0.05), and significantly decreased at 36h after operation (P<0.05).The peak value of the average number of AgNORs particles was delayed from 36h to 48h, and the average diameter of AgNORs particles was significantly increased at 36h-72h and 168h after operation (P<0.05). The peak value of the average diameter of AgNORs particles was delayed from 24h-48h to36h-48h; The average number of AgNORs particles in PHT group rats was significantly incresed at 24h and 48h after operation (P<0.05), and was significantly lower at 36h after operation (P<0.05), The peak value of the average number of AgNORs particles were delayed from 36h to 48h. The average diameter of AgNORs particles was significantly increased at 24h-168h after operation (P<0.05). (3) The number of PCNA positive hepatocytes: Compared with PH group , the average number of PCNA positive hepatocytes in PHS group rats was decreased at each time point , and significantly lower at 24h～48h and 168h after operation (P<0.05); the average number of PCNA positive hepatocytes in PHV group rats was increased at each time point , and significantly increased at 24h, 72h, and 120h after operation (P<0.05); the average number of PCNA positive hepatocytes in PHT group rats was increased at each time point, and significantly increased at12-36h and 72-168h after operation (P <0.05). (4) Serum estrogen levels: Compared with PH group , serum estrogen levels in PHS group rats was significantly decreased at 12h-24h and120h-168h after operation (P<0.05). Serum estrogen levels in PHV group rats was significantly increased at 12h-36h after operation ,and significantly decreased at 120h-168h after operation (P<0.05) . Serum estrogen levels in PHT group rats was significantly increased at 12h-24h after operation ,and significantly decreased at 36h-168h after operation (P<0.05) . (5) MMP-9 expression of hepatocytes : Compared with PH group , MMP-9 expression in PHS group rats was significantly decreased at 24h-48h and 120h after operation (P<0.05), but it was significantly increased at 72h after operation (P<0.05); MMP-9 expression in PHV group rats was increased at 12h-168h after operation , and significantly increased at 12h-120h after operation (P<0.05) ; MMP-9 expression in PHT group rats was increased at 12h-168h after operation ,and significantly increased at 12h,72h,120h after operation (P<0.05).Conclusion:(1)Hepatic sympathetic denervation can inhibit liver regeneration at 12h-120h after operation and promote liver regeneration at 168h after operation; Hepatic vagotomy can promote liver regeneration at 12h-120h after operation; Total hepatic denervation can promote liver regeneration at 12h-168h after operation(.2)The regulative effect of denervation on liver regeneration may be triggered by adjusting serum estrogen levels to regulate hepatocytes proliferation and by adjusting the MMP-9 expression of hepatocytes to regulate hepatic tissue reconstruction.