Therapeutic Effect and Mechanism of Paeoniae Radix Rubra and Sargentodoxae Caulis in Delaying Salivary Gland Injury in Sjögren's Syndrome

LIU Ruihua; TANG Xiaopo; GUO Zilin; YANG Kefei; LIU Wenjing; ZHOU Xinyao; JIANG Quan

Abstract：Objective To observe the therapeutic effects of Paeoniae Radix Rubra and Sargentodoxae Caulis on salivary gland injury in Sjögren's syndrome(SS),and to explore the biological mechanism of delaying the gland injury by regulating the imbalance of Follicular helper T cell(Tfh)and Regulatory cell(Treg)through interleukin(IL)-2.Methods Female NOD mice were randomly divided into 5 groups:model group,Paeoniae Radix Rubra group,Sargentodoxae Caulis group,Paeoniae Radix Rubra and Sargentodoxae Caulis group,and IL-2 group,with 10 mice in each group.10 female BALB/c mice were used as the normal group.Intervention was initiated at the age of 9 weeks,and Paeoniae Radix Rubra group,Sargentodoxae Caulis group,Paeoniae Radix Rubra and Sargentodoxae Caulis group were respectively given the decoction of Paeoniae Radix Rubra,Sargentodoxae Caulis,Paeoniae Radix Rubra and Sargentodoxae Caulis by gastric gavage once a day,and IL-2 group was given the recombinant human IL-2 by subcutaneous injection once every other day,and normal group and model group were given physiological saline by gavage once a day.Each group was intervened for a total of 3 weeks.During the intervention period,observe the general situation,water intake,and the saliva flow of each group of mice.After the intervention,HE staining was used to evaluate the pathological changes in the submandibular gland,immunohistochemistry was used to detect the expression of IL-2 in the submandibular gland,and flow cytometry was used to detect the levels of Tfh and Treg cells in the spleen.Results Compared with the normal group,the model group had significantly higher water intake(P<0.05),lower salivary flow rate(P<0.05),increased pathological grade of the submandibular gland(P<0.05),lower expression of IL-2 in the submandibular gland,elevated ratio of splenic Tfh/Treg cells.Compared with model group,the Paeoniae Radix Rubra group,Sargentodoxae Caulis group,Paeoniae Radix Rubra and Sargentodoxae Caulis group,and IL-2 group has significantly lower water intake(P<0.05),higher salivary flow rate(P<0.05),decreased pathological grade of submandibular gland(P<0.05),higher expression of IL-2 in the submandibular gland,and down-regulated ratio of splenic Tfh/Treg cells(P<0.05),and there was no significant difference in the comparison of the treatment groups(P>0.05).Conculsion Paeoniae Radix Rubra and Sargentodoxae Caulis were able to attenuate lymphocyte infiltration in the submandibular gland of NOD mice,improve the structure and function of the gland,and increase salivary secretion.Paeoniae Radix Rubra and Sargentodoxae Caulis may play their therapeutic roles in SS by regulating IL-2 levels and restoring Tfh and Treg homeostasis.