Mutations in the IARS1 gene are rare in clinical practice， and up to now， only ten cases with detailed clinical and genetic data have been recorded in the literature. This article reports a case of growth retardation， intellectual developmental disorder， hypotonia， and hepatopathy （GRIDHH） associated with single heterozygous mutations in the IARS1 gene and summarizes the clinical and genetic features of GRIDHH， thereby expanding the genetic spectrum of GRIDHH.

ObjectiveTo investigate the mechanism by which modified Shengjiangsan （MSJS） improves diabetic kidney disease （DKD） by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar， high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. After successful modeling， the rats were randomly divided into six groups： a normal control group， a model group， low-， medium-， and high-dose MSJS groups （7.7， 15.4， 30.8 g·kg^-1， respectively）， and an irbesartan group （0.384 g·kg^-1）. Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose， body weight， and kidney weight were recorded. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to determine urinary microalbumin （mALB）， and serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Histopathological changes in renal tissues were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy （TEM）. The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta （LC3B） and cytochrome c oxidase subunit Ⅳ （COX Ⅳ）. ResultsCompared with the normal control group， the model group exhibited significant increases in renal index， blood glucose， and 24-hour urinary microalbumin （24 h mALB） （P<0.05， P<0.01）. The levels of serum SCr and BUN were significantly elevated （P<0.01）， and the serum levels of TNF-α， IL-1β， and IL-6 were markedly upregulated （P<0.01）. Histopathological examination revealed glomerular hypertrophy， mesangial expansion and increased deposition， podocyte foot process flattening and fusion， a decreased number of autophagosomes accompanied by mitochondrial swelling， vacuolar degeneration of renal tubular epithelial cells， and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B， PTEN-induced putative kinase 1 （PINK1）， and E3 ubiquitin-protein ligase （Parkin） were significantly decreased （P<0.05， P<0.01）， while expression of the selective autophagy adaptor protein p62 was significantly increased （P<0.01）. Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group， the MSJS treatment groups and the irbesartan group showed significant reductions in renal index， blood glucose， and 24 h mALB （P<0.05， P<0.01）. The serum SCr and BUN levels decreased significantly （P<0.05） and TNF-α， IL-1β， and IL-6 levels were significantly downregulated （P<0.05， P<0.01）. Histopathological damage was alleviated， including reduced glomerular hypertrophy， decreased mesangial deposition， and attenuated podocyte foot process fusion. The number of autophagosomes increased， and mitochondrial swelling was improved. The expression levels of LC3B， PINK1， and Parkin in renal tissues were significantly upregulated， whereas p62 expression was significantly downregulated （P<0.05， P<0.01） in MSJS groups. Immunofluorescence signal intensity was enhanced， and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.

ObjectiveTo investigate the mechanism by which modified Shengjiangsan （MSJS） improves diabetic kidney disease （DKD） by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar， high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. After successful modeling， the rats were randomly divided into six groups： a normal control group， a model group， low-， medium-， and high-dose MSJS groups （7.7， 15.4， 30.8 g·kg^-1， respectively）， and an irbesartan group （0.384 g·kg^-1）. Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose， body weight， and kidney weight were recorded. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to determine urinary microalbumin （mALB）， and serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Histopathological changes in renal tissues were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy （TEM）. The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta （LC3B） and cytochrome c oxidase subunit Ⅳ （COX Ⅳ）. ResultsCompared with the normal control group， the model group exhibited significant increases in renal index， blood glucose， and 24-hour urinary microalbumin （24 h mALB） （P<0.05， P<0.01）. The levels of serum SCr and BUN were significantly elevated （P<0.01）， and the serum levels of TNF-α， IL-1β， and IL-6 were markedly upregulated （P<0.01）. Histopathological examination revealed glomerular hypertrophy， mesangial expansion and increased deposition， podocyte foot process flattening and fusion， a decreased number of autophagosomes accompanied by mitochondrial swelling， vacuolar degeneration of renal tubular epithelial cells， and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B， PTEN-induced putative kinase 1 （PINK1）， and E3 ubiquitin-protein ligase （Parkin） were significantly decreased （P<0.05， P<0.01）， while expression of the selective autophagy adaptor protein p62 was significantly increased （P<0.01）. Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group， the MSJS treatment groups and the irbesartan group showed significant reductions in renal index， blood glucose， and 24 h mALB （P<0.05， P<0.01）. The serum SCr and BUN levels decreased significantly （P<0.05） and TNF-α， IL-1β， and IL-6 levels were significantly downregulated （P<0.05， P<0.01）. Histopathological damage was alleviated， including reduced glomerular hypertrophy， decreased mesangial deposition， and attenuated podocyte foot process fusion. The number of autophagosomes increased， and mitochondrial swelling was improved. The expression levels of LC3B， PINK1， and Parkin in renal tissues were significantly upregulated， whereas p62 expression was significantly downregulated （P<0.05， P<0.01） in MSJS groups. Immunofluorescence signal intensity was enhanced， and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.

OBJECTIVE To study the effects of peripheral blood-derived exosomes （Exo） intervened by Naozhenning （NZN） on injury of neuron cells HT22 induced by microglia BV-2 cells. METHODS Wistar rats were selected to prepare peripheral blood- derived Exo intervened by NZN （66.83 g/kg）， referred to as NZN-Exo； peripheral blood-derived Exo intervened by normal saline and piracetam （PLXT， 1.62 g/kg） were prepared using the same method， denoted as KB-Exo and PLXT-Exo respectively， and all Exo were subsequently identified. Meanwhile， BV-2 cells were stimulated with 1 μg/mL lipopolysaccharide （LPS） to prepare LPS- stimulated supernatant， and non-LPS-stimulated supernatant was prepared following the same protocol. HT22 cells were divided into four groups: KB-Exo group （treated with non-LPS-stimulated supernatant+KB-Exo）， model group （treated with LPS-stimulated supernatant+KB-Exo）， PLXT-Exo group （treated with LPS-stimulated supernatant+PLXT-Exo）， and NZN-Exo group （treated with LPS-stimulated supernatant+NZN-Exo）， with the concentration of the corresponding Exo in all groups being 50 μg/mL. After 24 hours of culture， the proliferation of HT22 cells was detected by the CCK-8 assay and EdU assay； the apoptosis of HT22 cells was detected； the microstructure of HT22 cells was observed； the contents of interleukin-1β （IL-1β）， IL-10， nuclear factor-κB （NF- κB）， and tumor necrosis factor-α （TNF-α） in HT22 cells were measured， as well as the expression levels of TNF-α， NOD-like receptor thermal protein domain associated protein 3 （NLRP3）， Caspase-1， B-cell lymphoma-2（ Bcl-2）， and Bcl-2-associated X protein （Bax）. RESULTS KB-Exo， PLXT-Exo and NZN-Exo were successfully prepared， and all Exo exhibited typical cup-shaped contours and membrane-enclosed characteristics. Compared with KB-Exo group， model group showed significantly decreased cell proliferation rates （detected by CCK-8 and EdU）， intracellular IL-10 levels， and Bcl-2 protein expression levels （P＜0.05）； while the cell apoptosis rate， intracellular levels of IL-1β， TNF-α， and NF-κB， as well as the expression levels of NLRP3， TNF-α， Caspase-1， and Bax proteins were significantly increased （P＜0.05）. Additionally， in the model group， the cells showed volume swelling， incomplete cell membrane， nucleolar rupture， significant swelling and deformation of mitochondria， and severe vacuolization. Compared with model group， the above quantitative indicators in the PLXT-Exo group and NZN-Exo group were significantly reversed （P＜0.05）， with large and round cell nuclei， intact nuclear membranes， and reduced mitochondrial vacuolization. CONCLUSIONS Peripheral blood-derived Exo intervened by naozhenning can alleviate the injury of neuronal cells HT22 by inhibiting inflammatory responses and cell apoptosis.

OBJECTIVE: To observe the effects of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on myocardial transferrin receptor 1 (TfR1), ferroptosis suppressor protein 1 (FSP1), atrial natriuretic peptide (ANP), and typeⅠcollagen myocardial collagen fibers (CollagenⅠ) in rats with chronic heart failure (CHF), and to explore the mechanism of moxibustion for ameliorating myocardial fibrosis and improving cardiac function in CHF. METHODS: Fifty SD rats were randomly divided into a normal group (n=10) and a modeling group (n=40). The CHF model was established in the modeling group by ligating the left anterior descending coronary artery. After successful modeling, the rats were randomly divided into a model group (n=9), a moxibustion group (n=8), a rapamycin (RAPA) group (n=9), and a moxibustion+RAPA group (n=9). In the moxibustion group, moxibustion was delivered at bilateral "Feishu"(BL13) and "Xinshu" (BL15), 15 min at each point in each intervention, once daily, for 4 consecutive weeks. In the RAPA group, RAPA solution was administered intraperitoneally at a dose of 1 mg/kg, once daily for 4 consecutive weeks. In the moxibustion+RAPA group, RAPA solution was administered intraperitoneally after moxibustion. Ejection fraction (EF) and left ventricular fractional shortening (FS) were measured after modeling and intervention. After intervention, morphology of cardiac muscle was observed using HE staining and Masson's trichrome staining. Total iron content in myocardial tissue was detected using a colorimetric method. Western blot and qPCR were adopted to detect the protein and mRNA expression of TfR1, FSP1, ANP, and CollagenⅠ in myocardial tissue. RESULTS: Compared with the normal group, the EF and FS values decreased (P<0.01); necrosis, edema, degeneration, and arrangement disorder were presented in cardiomyocytes; inflammatory cells were obviously infiltrated, the structure of myocardial fibers was disarranged, the collagen fibers were obviously deposited and fibrosis increased (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue were elevated (P<0.01), while the protein and mRNA expression of FSP1 were reduced (P<0.01) in the model group. Compared with the model group, the moxibustion group showed that EF and FS increased (P<0.01); myocardial cell morphology was improved, and myocardial fibrosis was alleviated (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while the protein and mRNA expression of FSP1 increased (P<0.01, P<0.05). Compared with the model group, the myocardial fibrosis was increased (P<0.05); the total iron content and the protein and mRNA expression of TfR1, ANP, CollagenⅠ in myocardial tissue were increased (P<0.01), while protein and mRNA expression of FSP1 decreased (P<0.01) in the RAPA group. When compared with the RAPA group and the moxibustion + RAPA group, EF and FS were elevated (P<0.01, P<0.05); myocardial cells were improved in morphology, the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while protein and mRNA expression of FSP1 increased (P<0.01) in the moxibustion group. In comparison with the moxibustion + RAPA group, the RAPA group showed the decrease in EF and FS (P<0.01), the worsened myocardial fibrosis (P<0.01), the increase in the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue (P<0.01), and the decrease in the protein and mRNA expression of FSP1 (P<0.01). CONCLUSION Moxibustion at "Feishu" (BL13) and "Xinshu" (BL15) can slow down the process of myocardial fibrosis and improve cardiac function in CHF rats. The mechanism of moxibustion may be related to inhibiting ferroptosis through regulating autophagy.
Animals ; Rats ; Heart Failure/physiopathology* ; Moxibustion ; Rats, Sprague-Dawley ; Male ; Receptors, Transferrin/genetics* ; Myocardium/metabolism* ; Acupuncture Points ; Humans ; Chronic Disease/therapy* ; Antigens, CD/metabolism*

OBJECTIVE: To observe the effects of moxibustion at "Feishu" (BL13) and "Xinshu" (BL15) on the circular RNA of exon 2-5 of the Pan3 gene (circPAN3), forkhead box O3 (FOXO3), and Bcl-2/adenovirus E1B19kDa-interacting protein 3 (BNIP3) in rats with chronic heart failure (CHF), and explore the potential mechanisms of moxibustion in alleviating myocardial fibrosis. METHODS: Ten rats of 60 male SPF-grade SD rats were randomly assigned into a normal group. The remaining rats underwent left anterior descending coronary artery (LAD) ligation to establish the CHF model. Forty successfully modeled rats were randomly divided into a model group, a moxibustion group, a rapamycin (RAPA) group, and a moxibustion+RAPA group, with 10 rats in each group. The moxibustion group received mild moxibustion at bilateral "Feishu" (BL13) and "Xinshu" (BL15), 30 min per session. The RAPA group received intraperitoneal injection of the autophagy activator RAPA (1 mg/kg). The moxibustion+RAPA group first received RAPA injection, followed by mild moxibustion at bilateral "Feishu" (BL13) and "Xinshu" (BL15). All interventions were administered once daily for 4 consecutive weeks. After the intervention, cardiac ultrasound was used to measure ejection fraction (EF) and left ventricular fractional shortening (FS). Serum placental growth factor (PLGF) level was determined by ELISA. Myocardial tissue morphology and collagen volume were assessed using hematoxylin-eosin (HE) staining and Masson's trichrome staining. The expression levels of circPAN3, FOXO3, and BNIP3 mRNA in myocardial tissue were detected by real-time PCR, while FOXO3 and BNIP3 protein expression levels were analyzed by Western blot. RESULTS: Compared with the normal group, the model group exhibited myocardial cell disorder, severe fibrosis, and increased collagen volume (P<0.01), along with significantly decreased EF, FS, and circPAN3 mRNA expression in myocardial tissue (P<0.01), and the serum PLGF level, as well as FOXO3 and BNIP3 mRNA and protein expression in myocardial tissue were increased (P<0.01). Compared with the model group, the moxibustion group showed reduced myocardial fibrosis, decreased collagen volume (P<0.01), increased EF, FS, and circPAN3 mRNA expression in myocardial tissue (P<0.01), and decreased serum PLGF level as well as FOXO3 and BNIP3 mRNA and protein expression in myocardial tissue (P<0.01). Compared with the model group, the RAPA group showed further deterioration in these parameters (P<0.01). Compared with the RAPA group, the moxibustion+RAPA group exhibited alleviation of myocardial fibrosis, reduced collagen volume (P<0.01), increased EF, FS, and circPAN3 mRNA expression in myocardial tissue (P<0.01), and decreased serum PLGF level as well as FOXO3 and BNIP3 mRNA and protein expression in myocardial tissue (P<0.01). CONCLUSION Moxibustion could alleviate myocardial fibrosis in CHF rats, possibly through upregulation of myocardial circPAN3 expression, downregulation of FOXO3 and BNIP3 expression, and inhibition of excessive myocardial autophagy.
Animals ; Moxibustion ; Heart Failure/metabolism* ; Male ; Rats ; Rats, Sprague-Dawley ; Myocardium/pathology* ; RNA, Circular/metabolism* ; Membrane Proteins/metabolism* ; Forkhead Box Protein O3/metabolism* ; Acupuncture Points ; Humans ; Fibrosis/genetics* ; Chronic Disease/therapy* ; Mitochondrial Proteins

Lymph node metastasis (LNM) is a crucial risk factor influencing an unfavorable prognosis in specific cancers. Fundamental research illuminates our understanding of tumor behavior and identifies valuable therapeutic targets. Nevertheless, the exploration of fundamental theories and the validation of clinical therapies hinge on preclinical experiments. Preclinical models, in this context, serve as the conduit connecting fundamental theories to clinical outcomes. In vivo models established in animals offer a valuable platform for comprehensively observing interactions between tumor cells and organisms. Using various experimental animals, including mice, diverse methods, such as carcinogen-induced tumorigenesis, tumor cell line or human tumor transplantation, genetic engineering, and humanization, have been used effectively to construct numerous models for tumor LNM. Carcinogen-induced models simulate the entire process of tumorigenesis and metastasis. Transplantation models, using human tumor cell lines or patient-derived tumors, offer a research platform closely mirroring the histology and clinical behavior of human tumors. Genetically engineered models have been used to delve into the mechanisms of primary tumorigenesis within an intact microenvironment. Humanized models are used to overcome barriers between human and murine immune systems. Beyond mouse models, various other animal models have unique advantages and limitations, all contributing to exploring LNM. This review summarizes existing in vitro and animal preclinical models, identifies current bottlenecks in preclinical research, and offers an outlook on forthcoming preclinical models.
Animals ; Humans ; Mice ; Lymphatic Metastasis/pathology* ; Disease Models, Animal ; Cell Line, Tumor

ObjectiveTo investigate the mechanism of astragaloside-Ⅳ （AS-Ⅳ） in regulating pyroptosis to alleviate intestinal ischemia-reperfusion injury （IRI） by combining network pharmacology and in vivo experiments. MethodFirstly， the corresponding target genes of AS-Ⅳ were obtained from TraditionalChineseMedicineSystemsPharmacology（TCMSP） database and Swiss Target Prediction database， and the target genes related to intestinal IRI and Pyroptosis were obtained from GeneCards database， and the common target genes of the three were obtained by drawing Venn diagrams through unspiralized website. Protein-protein interaction （PPI） network was constructed by STRING database and Cytoscape software to screen common target genes and imported into Cytoscape software to obtain core target genes. Microbiotics platform was used for gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis and prediction of the mechanism of action of AS-Ⅳ in regulating Pyroptosis to alleviate intestinal IRI. Then C57/BL6J mice were randomly divided into 5 groups normal group， model group（IR）， drug administration group （IR+AS-Ⅳ）， nucleotide-binding oligomerization structural domain-like receptor protein 3 （NLRP3） agonist NSS group （IR+AS-Ⅳ+NSS）， and NLRP3 inhibitor MCC950 group （IR+AS-Ⅳ+MCC950） by using a randomized numerical table method. The intestinal IRI model was established by clamping the superior mesenteric artery for 45 min and resuming perfusion for 2 h in the model group， the drug administration group， the NLRP3 agonist NSS group， and the NLRP3 inhibitor MCC950 group， and the normal group was only separated from the vessels without clamping. The administration group， the NLRP3 agonist NSS group， and the NLRP3 inhibitor MCC950 group were gavaged with astragaloside dissolved in 0.1% dimethylsulfoxide （50 mg·kg^-1） for 3 consecutive days before modeling， with the last gavage 2 h before modeling， and the remaining two groups were gavaged with equal amounts of saline. The NLRP3 agonist NSS group was injected intraperitoneally with 4 mg·kg^-1 of NSS 1 h before modeling， and the NLRP3 inhibitor MCC950 group was injected intraperitoneally with 10 mg·kg^-1 of MCC950 1 h before modeling.The mice were put to death by reperfusion for 2 h， and intestinal tissues were obtained. The levels of IL-18 and IL-1β were detected by enzyme linked immunosorbent assay（ELISA）， and the protein expression of thioredoxin-binding protein （TXNIP）， NLRP3， Caspase-1 and pyrocatechin D （GSDMD） were detected by Western blot， and the pathological changes of intestinal tissues were evaluated by Chiu's score. ResultNetwork pharmacological analysis showed that there were 1599 targets of intestinal IRI， 199 targets of AS-Ⅳ action， 197 targets of pyroptosis， and 20 targets common to all three. There were 10 core targets， including NLRP3， TXNIP， silencing information regulator 1 （SIRT1）， high mobility group protein 1 （HMGB1）， interleukin-18 （IL-18）， GSDMD， and metallo matrix protease-9 （MMP-9），et al. The results of in vivo experiments showed that compared with the normal group， Chiu's score was elevated in the model group， the levels of IL-18，IL-1β inflammatory factors in mouse intestinal tissues were elevated （P<0.05）， and the protein expression levels of TXNIP， NLRP3， Caspase-1， and GSDMD were elevated （P<0.05）. Compared with the model group，Chiu's score was decreased in the administered group and NLRP3 inhibitor MCC950 group，the level of IL-18，IL-1β inflammatory factors in the intestinal tissue of mice was decreased（P<0.05）， and the level of TXNIP，NLRP3，Caspase-1，GSDMD protein expression was decreased（P<0.05）. Compared with the administered group， Chiu's score was elevated in the NLRP3 agonist NSS group， the levels of IL-18， IL-1β inflammatory factors in mouse intestinal tissues were elevated （P<0.05）， and the protein expression levels of NLRP3， Caspase-1， and GSDMD were elevated （P<0.05）. Compared with the NLRP3 inhibitor MCC950 group， the NLRP3 agonist NSS group had elevated Chiu's scores， elevated levels of IL-18，IL-1β inflammatory factors in mouse intestinal tissues （P<0.05）， and elevated levels of TXNIP，NLRP3， Caspase-1， and GSDMD protein expression （P<0.05）. ConclusionNetwork pharmacological predictions were consistent with the results of in vivo experiments， and astragaloside attenuated intestinal ischemia-reperfusion injury by inhibiting cellular pyroptosis through the TXNIP-NLRP3 signaling pathway.

OBJECTIVE To explore the mechanism of Naozhenning granules in regulating mitochondrial energy metabolism in hippocampal tissue of multiple cerebral concussion （MCC） model rats. METHODS SPF grade Wistar rats were used to prepare MCC models using the “free fall impact method”. The successfully modeled rats were divided into model group， piracetam group， and Naozhenning granule low-dose， medium-dose and high-dose groups， and a normal group was also set up， with 8 rats in each group. Rats in each treatment group orally administered corresponding drugs at doses of 0.324 g/kg for the piracetam group and 2.25， 4.5 and 9 g/kg for the Naozhenning granule low-dose， medium-dose and high-dose groups； the normal group and model group were given equal volumes of normal saline； once a day， for 14 consecutive days. The motor exploration ability， learning and memory ability of rats were tested； the adenosine triphosphate （ATP） content in the hippocampal tissue of rat was detected； the changes in the mitochondrial structure of hippocampal tissue was observed； the fluorescence intensity of mitochondrial dynamin- related protein 1 （Drp1）， mitochondrial fission protein 1 （Fis1）， mitochondrial fusion 1 （Mfn1）， and optic atrophy protein 1 （Opa1） were detected in the hippocampal tissue of rat； the protein expression levels of peroxisome proliferator activated receptor gamma coactivator-1α（PGC-1α）， nuclear respiratory factor-1（NRF-1），mitochondrial transcription factor A（TFAM）， Wnt-3a，β-catenin in hippocampal tissue of rat were detected. RESULTS Compared with the normal group， the total exercise distance， number of central grid entries， number of upright positions， new object recognition index， mitochondrial ATP content， fluorescence intensity of Mfn1 and Opa1， the protein expression levels of PGC-1α、NRF-1、TFAM、Wnt-3a、 β-catenin in the model group were significantly reduced （P＜0.01）， while the rest time and fluorescence intensity of Drp1 and Fis1 in hippocampal tissue were significantly increased （P＜0.01）. The results of transmission electron microscopy showed that the mitochondria in the hippocampal tissue were significantly swollen， with a large number of broken and reduced cristae， and some mitochondria had myeloid changes in the membrane. Compared with the model group， the levels/contents of the above indicators in rats of each administration group showed varying degrees of reversal， and most of the differences were statistically significant （P＜0.05 or P＜0.01）； the degree of mitochondrial swelling in the hippocampal tissue was reduced， with a small amount of broken and reduced cristae， fuzzy fractures appeared in local areas of the rough endoplasmic reticulum. CONCLUSIONS Naozhenning granules can improve the motor exploration， learning and memory abilities of MCC model rats， repair neuronal damage， and exert neuroprotective effects. Its mechanism may be related to activating Wnt/β-catenin signaling pathway，maintaining the balance of mitochondrial division and fusion，and promoting mitochondrial biosynthesis.