Effects Of Recombinant Ganoderma Lucidum Immunoregulatory Protein On A Mouse Model Of Parkinson’s Disease And Its Mechanism’s Study

Fungal Immunomodulatory Protein of Ganoderma lucidium (LZ-8) was aImmunomodulatory Protein isolated from extract of Ganoderma mycelium. Studieshad found that it has the biological activity of promoting lymphocyte proliferation,inhibiting systemic anaphylaxis, suppressing rejection after organ transplantation andinhibiting tumor growth. The recombinant Ganoderma lucidum immunoregulatoryprotein (rLZ-8) used in this paper was the samples obtained from Pichia pastoris, inwhich the recoded gene of LZ-8expressed using genetic engineering methods.Parkinson’s disease (PD) is one of the most common neurodegenerative diseasesin the elders. Its main pathological feature is progressive degeneration of dopaminer-gic neurons in the substantia nigra pars compacta. In the field of its pathogenesis’study, reseachers focus on oxidative stress injury and neuroinflammation in recentyears. Studies has observed oxidative stress, changes in the leves of various cytokines,as well as changes in activity and the number of glial cells in PD patients. The studyalso confirmed that using anti-inflammatory drugs may protect dopamine neurons inthe substantia nigra. Therefore design this article to explore whether rLZ-8has aprotective effect on PD and whether rLZ-8play its role through inhibiting oxidativestress and inflammatory response.120C57BL/6mice were randomly divided into six groups: control group, modelgroup, madopar group(positive drug group), rLZ-8low dosage group, rLZ-8middledosage group, and rLZ-8high dosage group. Each group had20mice. Mice receivedintraperitoneal injections of30mg/kg/day MPTP over5consecutive days to inducethe model of PD.9days before MPTP injection, mice in control group and modelgroup received saline by intraperitoneal injection, and mice in positive drug groupreceived madopar by intragastric administration, and mice in rLZ-8low, middle andhigh dose group received rLZ-860μg/kg,100μg/kg and160μg/kg. The administrationlasted to7days after last MPTP treatment.7days after last MPTP treatment, mice ineach group were performed behavioral experiments: pole test, traction test, and rotarod test. After behavioral experiments, we used immunohistochemistry to assaythe expression of tyrosine hydroxylase. Then we used ELISA method to assay thecontents of Interleukin-1β(IL-1β) and Interleukin-6(IL-6), and used colorimetry toassay the activities of superoxide dismutase (SOD) and malondialdehyde (MDA) andcontent of glutathione peroxidase (GSH-Px).Behavioral experiments showed that rLZ-8could reduce the time of PD micetaken to turn head downward and the time until the mice reached the floor, extendsuspension time and improve the suspension situation, extend time that miceremained on the rod and reduce the falling number. rLZ-8could also significantlyincrease the number of TH immunopositive neurons in substantia nigra and thedensity of TH immunopositive fibers in striatum. rLZ-8could significantly decreasethe contents of IL-1β and IL-6in substantia nigra. In addition, rLZ-8couldsignificantly enhance the activities of SODand GSH-Px, and reduce the content ofMDA.In conclusion, the present study demonstrated that rLZ-8exhibited protectiveeffect on PD mouse model, it could ameliorate impairment of behavior as well asresist MPTP-induced loss of dopaminergic neurons. These effects appeared to becorrelated with inhibiting oxidative stress and inhibiting inflammatory response. Inconcert, these data suggested that rLZ-8was a promising, clinically applicableapproach for the treatment of PD.