Objective To investigate the effect and mechanism of interfering the nicotinamide mononucleotide adenylyltransferase 1(NMNAT1)gene in Parkinson's disease(PD)mouse models. Methods Thirty mice were randomly assigned to three groups: the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)group, the small interfering nicotinamide mononucleotide adenylyltransferase 1 (siNMNAT1)+MPTP group, and the control group, with 10 mice in each group.After injecting siRNA-green fluorescent protein(GFP)lentivirals directly into substantia nigra(SN),mice received intraperitoneal injections of MPTP, which was the siNMNAT1 +MPTP group.While the MPTP group was only with injections of MPTP,and the control group was with neither siRNA nor MPTP.Then we assessed the motor coordination ability firstly.To observe the variation of nigrostriatal pathway, the counts of dopamanergic neurons in SN were measured by tyrosine hydroxylase(TH)immunofluorescence staining.And the expression of TH in striatum, which was used to estimate the dopaminergic neurons axonal variation, was analyzed by RT-PCR.Then the expression of TH, SOD1, Bcl2, Bax, Bcl2/Bax in SN was estimated through Western blotting.Results Compared with the control group,the siNMNAT1+MPTP group and the MPTP group decreased significantly in motor coordination ability(creep down time: siNMNAT1 +MPTP group(62.8 ±15.7)s,MPTP group(77.9 ±13.5)s, control group(122.0 ±25.2)s), dopamanergic neuron counts(siNMNAT1 +MPTP group 45.0 ±6.7, MPTP group 68.0 ±11.3, control group 93.0 ± 12.8)and the striatal TH expression(Creep down time: t=-6.291, P=0.000; t=-4.865, P=0.000.Dopamanergic neuron counts:t=-10.482,P=0.000;t=-4.624, P=0.000.TH expression:t=-9.117,P=0.000;t=-5.716, P=0.000).Although the siNMNAT1+MPTP group showed lower coordination ability than the MPTP group, there was no statistically significant difference.Whereas the counts of dopamanergic neurons in SN(t=-5.487, P=0.000), the expression of TH in striatum(t=-5.146,P=0.003),SOD1(t=-4.143, P=0.001)and Bcl2/Bax(t=-6.303, P=0.000)were obviously decreased in the siNMNAT1+MPTP group,in which Bax increased significantly(t=3.550,P=0.002).Conclusions Interfering the expression of NMNAT1 aggravated the neurodegeneration in PD, and the mechanism might be related to oxidative stress and programmed cell death.

Tuoli Xiaodusan is the 65^th formula in the Catalogue of Ancient Famous Classical Formulas（First Batch）. In this study， the bibliometric method was used to summarize and verify the ancient books about Tuoli Xiaodusan in terms of its historical origin， composition and dosage of the formula， indications， decoction and administration method， and processing， etc. According to the research， there is no definite date of the formation of Tuoli Xiaodusan， the earliest can be traced back to Lizhai Waike Fahui in Ming dynasty， which has been widely circulated， with many versions of prescription composition， and the modern influential version is from Waike Zhengzong in Ming dynasty， which is made up of 12 Chinese herbs including Ginseng Radix et Rhizoma（3.73 g）， Chuanxiong Rhizoma（3.73 g）， Paeoniae Radix Alba（3.73 g）， Astragali Radix（3.73 g）， Angelicae Sinensis Radix（3.73 g）， Atractylodis Macrocephalae Rhizoma（3.73 g）， Poria（3.73 g）， Lonicerae Japonicae Flos（3.73 g）， Angelicae Dahuricae Radix（1.87 g）， Glycyrrhizae Radix et Rhizoma（1.87 g）， Gleditsiae Spina（1.87 g）， Platycodonis Radix（1.87 g）. The herb origins almost follow the 2020 edition of Chinese Pharmacopoeia， except that Angelica dahurica var. formosana is only recommended as the origin of Angelicae Dahuricae Radix， and Glycryyhiza uralensis is only recommended as the origin of Glycyrrhizae Radix et Rhizoma. All the herbs are recommended to be used in the raw products. As for the preparation method， it is recommended to decoct with water， add 400 mL of water， boil until 160 mL， and take 2-3 times a day. The formula has the functions of nourishing Qi and nourishing blood， detoxifying and draining pus， and was mainly used to treat ulcerative diseases with the syndrome of syndrome of healthy Qi deficiency and pathogenic factors excess in ancient times， and in modern times， it is used for a wide range of treatment， involving the skin and soft tissues， bones， digestion and many other systemic diseases， and is also mainly used for syndrome of healthy Qi deficiency and pathogenic factors excess. In this study， the ancient and modern applications of Tuoli Xiaodusan were summarized， and its key information was identified， providing a basis for its wider clinical application， in-depth research and formulation development.