Intervention effect and mechanism of Jianpi Bushen Formula on amyotrophic lateral sclerosis mouse
Objective To explore the effect of Jianpi Bushen Formula on motor function of amyotrophic lateral sclerosis(ALS)model mice and its mechanism.Methods Twelve ADAR2flox/flox/VAChT-Cre mice(AR2 mice)produced by transgenic method to retain part of the motor function were divided into the model group and the treatment group,with 6 mice in each group;6 wild-type(WT)mice from the same batch were used as the control group.The mice in the treatment group were given Jianpi Bushen Formula[30 g/(kg·d)]by intragastric administration,while the mice in the control and model groups received 0.2 mL of sodium chloride solution(9 g/L)by intragastric administration once a day for 8 consecutive weeks.Mice were observed weekly for activity,body mass,and behavioral functions such as grip strength and fatigue resistance(roller test).Following a 24-week period,the mice were subjected to sampling,with the anterior horn of the spinal cord undergoing staining with both haematoxylin-eosin(HE)and Nissl stainings,in order to observe the histopathological changes in the aforementioned region of the spinal cords of the mice in all experimental groups.The protein expression of adenosine deaminase acting on RNA 2(ADAR2)and TAR DNA-binding protein 43(TDP-43)in the tissues of each group was detected by Western blot,and the ultrastructural changes of the anterior horn in each group were detected by transmission electron microscopy.Results In comparison to the control group,the body mass of mice in the model group exhibited a gradual increase with age,whereas the body mass in the treatment group demonstrated a decline in comparison to the model group.Compared with the control group,the anti-fatigue degree of mice in the model group and the treatment group decreased.However,the decline in anti-fatigue capacity observed in the treatment group occurred at a later stage in comparison to the model group.In comparison to the control group,the model group of mice exhibited a reduction in grip strength,with the decline in grip strength in the treatment group occurring at a relatively slower rate than that observed in the model group.The expression of TDP-43 was found to be significantly lower in the model group when contrasted with the control group(P<0.001).The treatment group exhibited elevated TDP-43 expression when contrasted with the model group(P<0.05).ADAR2 expression was observed to be significantly lower in the model group when contrasted with the control group(P<0.01),but no significant difference in ADAR2 expression was noted between the treatment group and the model group(P>0.05).Compared with the control group,the model group had severe motor neuron damage in the anterior horn of the spinal cord,and the neuronal structure was incomplete;Compared with the model group,the apoptosis number of nerve cells was reduced in the treatment group.Transmission electron microscopy revealed a notable increase in mitochondrial swelling apoptosis and demyelination in the model group when compared to the control group.Additionally,the treatment group exhibited partial demyelination and mitochondrial swelling when compared to the control group;the number of nerve cells with swelling and apoptosis was observed to be reduced when compared to the model group.Conclusion Jianpi Bushen Formula can delay the hypokinesia in ALS model mice,reduce the apoptosis and damage of spinal cord motor neurons,prevent the production of TDP-43,an abnormal marker of sporadic ALS(sALS)pathology,and protect the myelinated nerve fibers and mitochondria of spinal cord neurons,so as to effectively delay the progression of the disease and the loss of function in ALS mice.
amyotrophic lateral sclerosisJianpi Bushen Formulamechanism of actionmouse modeltraditional Chinese herbal medicine research
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