Objective: To observe the effect of Tangluoning on RNA-dependent protein kinase (PKR)-like ER kinase (PERK) pathway related protein and mRNA expressions of diabetic peripheral neuropathy (DPN) rats and Schwann cells. Method: A total of sixty SD male rats were used. Except for the blank control group

the rest SD male rats were treated with high-fat diet combined with streptozotocin (STZ

35 mg·kg-1) to replicate the DPN rats model. The rats were randomly divided into model control group

trimethylamine oxide group

low-dose Tangluoning group and high-dose Tangluoning group. After 12 weeks of continuous administration

hematoxylin-eosin staining (HE) was adopted to observe the pathological changes in sciatic nerve under the microscope. Immunofluorescence staining was used to detect expressions of p-PERK

phosphorylated eukaryotic translation initiation factor 2α (p-eIF2a) and activating transcription factor 4 (ATF4) proteins in sciatic nerve; high-sugar-induced schwann cell model was established. The experiment was divided into 25 mmol·L-1 glucose group (control)

150 mmol·L-1 glucose group (model)

150 mmol·L-1 glucose+0.1%

1%

10% Tangluoning groups; they were respectively treated for 24

48 h. Real-time PCR was used to detect PERK

nuclear factor-E2-related factor 2 (Nrf2)

heme oxygenase-1 (HO-1)

B-cell lymphoma 2 associated X protein (Bax) and Caspase-3 mRNA expressions. Result: Pathological changes in sciatic nerve: myelinated nerve fiber had a complete dense structure and regular shape in blank control group; severe demyelination phenomenon

irregular shape and disordered arrangement were observed in model group; whereas mild demyelination phenomenon

approximately complete structure and approximately regular shape were found in Tangluoning groups. As for integral optical density

compared with the blank control group

model group exhibited a higher level (P<0.01); compared with model group

herb group exhibited a lower level (P<0.01). As for mRNA expressions of PERK

Nrf2

HO-1

Caspase 3 and Bax in Schwann cells

compared with control group

mRNA expression of PERK

Bax and Caspase 3 in model group were significantly increased (P<0.05

P<0.01); compared with model group

mRNA expressions of PERK

Caspase-3 and Bax in Tangluoning groups were significantly decreased (P<0.05

P<0.01)

and mRNA expressions of Nrf2 and HO-1 were significantly increased (P<0.05

P<0.01). As for protein expressions of p-PERK

p-eIF2a and ATF4

compared with blank control group

protein expressions of p-PERK

p-eIF2a and ATF4 in model group displayed an obvious increase (P<0.01); compared with model control group

Tangluoning groups displayed an obvious decrease (P<0.01). Conclusion: Tangluoning can alleviate the pathological damage of sciatic nerve tissues and regulate the PERK pathway

including down-regulating PERK/eIF2a/ATF4 pathway and up-regulating PERK/Nrf2/HO-1 pathway when endoplasmic reticulum stress (ERS) improves DPN.