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. 2020 Jun 30;11:988. doi: 10.3389/fphar.2020.00988

Table 2.

Characteristics of the 24 included studies.

(years) Species (Sex, n = experimental/control group) Weight Model (method) The Criteria for modeling successfully Anesthetic Treatment group (Method to astragal sides) Control group Outcome index (time) Intergroup differences
Gui et al., 2012 SD rats
(male, 8/8)
180–200 g By intraperitoneal injection of STZ (65 mg/kg) Rats with a blood glucose level over 300 mg/dl in 3 different times after 72 h of STZ injection Pentobarbital sodium By oral gavage of AS-IV (10 mg/kg, qd) in 2 weeks before STZ injection and lasted 14 weeks By oral gavage of an equal volume of CMC in 2 weeks before STZ injection and lasted 14 weeks 1. Renal pathology
2. BUN and SCr
3. HbA1c
4. BG
5. ALT
6. SOD and MDA
7. CAT
8. Caspase-3
9. Bax and Bcl-2
1. P < 0.05
2. P > 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05
7. P < 0.05
8. P < 0.05
9. P < 0.05
Chen et al., 2014 SD rats
(male, 8/8)
180–200 g By intraperitoneal injection of STZ (65 mg/kg) Rats with a blood glucose level over 300 mg/dl in 3 different times after 72 h of STZ injection Pentobarbital sodium By oral gavage of AS-IV (10 mg/kg, qd) in 2 weeks before STZ injection and lasted 14 weeks By oral gavage of an equal volume of CMC in 2 weeks before STZ injection and lasted 14 weeks 1. Renal pathology
2. 24-h urinary protein
3. BUN and SCr
4. BG
5. ALT and AST
6. Integrin α3, β1 subunits
and ILK
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05
Lu et al., 2015 SD rats
(male, 14/14)
180–220 g By intraperitoneal injection of STZ (125 mg/kg, qd) for 2 consecutive days Rats with a blood glucose level over 16.7 mmol/L in 3 different times after 72 h of STZ injection NM By oral gavage of AS-IV (40 mg/kg, qd) after STZ injection and lasted 8 weeks By oral gavage of an equal volume of NS after STZ injection and lasted 8 weeks 1. Renal pathology
2. 24-h urinary microalbumin
3. BG
4. integrin α4 and β1 subunits and ILK
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
Wang et al., 2015 SD rats
(male, 14/14)
180–200 g By intraperitoneal injection of STZ (50 mg/kg, qd) for 5 consecutive days Rats with a blood glucose level over 300 mg/dl in 3 different times after 72 h of STZ injection Pentobarbital sodium By oral gavage of AS-IV (10 mg/kg, qd) in 2 weeks after STZ injection and lasted 8 weeks By oral gavage of an equal volume of NS in 2 weeks after STZ injection and lasted 8 weeks 1. Renal pathology
2. 24-h urinary protein
3. BUN and SCr
4. Kidney/body weight ratio
5. BG
6. Total and phosphorylated PERK, eIF2a, and JNK
7. GRP78 and ORP150
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05
7. P < 0.05
Chen and Chen, 2016 SD rats
(male, 10/10)
180–200 g By intraperitoneal injection of STZ (40 mg/kg) Rats with a blood glucose level over 16.6 mmol/L in 3 different times after 72 h of STZ injection Chloral hydrate (35 mg/kg) By oral gavage of AS-IV (1 mmol/L, 5 ml, qd) after STZ injection and lasted 30 days By oral gavage of an equal volume of NS in after STZ injection and 30 days 1. Renal pathology
2. 24-h urinary protein
3. UCr
4. BG
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
Guo et al., 2016 db/db mice (male, 10/10) NM BKS.cg-m +/+ Leprdb/J mice (Spontaneous diabetes ) NM NM By oral gavage of AS-IV (18 mg/kg, qd) at 8 weeks of age and lasted 8 weeks By oral gavage of an equal volume of CMC at 8 weeks of age and lasted 8 weeks 1. Renal pathology
2. BUN and SCr
3. Kidney/body weight ratio
4. HbA1c
5. BG
6. HOMA-IR
7. TNF-α
8. MCP-1
9. Serum insulin
10. SERCA
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05
7. P < 0.05
8. P < 0.05
9. P < 0.05
10. P < 0.05
Huang et al., 2016 Wistar rats (male, 10/10) 170–230 g By intraperitoneal injection of STZ (60 mg/kg) Rats with a blood glucose level over 16.7 mmol/L and 24-h urinary protein level over 30mg/kg/d after 72 h of STZ injection Urethane (100mg/kg) By oral gavage of AS-IV (3 mg/kg, qd) after STZ injection and lasted 8 weeks By oral gavage of an equal volume of citrate buffer after STZ injection and lasted 8 weeks 1. 24-h urinary protein
2. BUN and SCr
3. BG
4. SOD, MDA, and GSH-Px
5. TGF-β1 mRNA
6. CAT mRNA
1.P<0.05
2.P<0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05
Li and Zhang, 2016 SD rats
(male, 10/10)
NM By intraperitoneal injection of STZ (60 mg/kg) Rats with a blood glucose level over 13.9 mg/kg after 1 week of STZ injection Pentobarbital sodium By oral gavage of AS-IV (1.08 g/kg, qd) after STZ injection and lasted 6 weeks By oral gavage of an equal volume of NS after STZ injection and lasted 6 weeks 1. Renal pathology
2. 24-h urinary microalbumin
3. Kidney/body weight ratio
4. BG
5. TGF-β1
6. Collagen I, II, III
7. α-SMA
8. TβRI, TβRII
9. Smad 2/3 and Smad 4
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05
7. P < 0.05
8. P < 0.05
9. P < 0.05
Ran and Ma, 2016 SD rats
(male, 10/10)
240–260 g By intraperitoneal injection of STZ (65 mg/kg) Rats with a blood glucose level over 16.7 mmol/L after 72 h of STZ injection NM By oral gavage of AS-IV (5 mg/kg, qd) after STZ injection and lasted 8 weeks By oral gavage of an equal volume of distilled water after STZ injection and lasted 8 weeks 1. Histological structure of kidney under transmission electron microscopy
2. 24-h urinary protein
3. 24-h urinary microalbumin
4. BG
5. Adiponectin
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
Sun et al., 2016 db/db mice (male, 8/8) NM BKS.Cg-Dock7m +/+Leprdb/JNju) mice (Spontaneous diabetes ) NM NM By oral gavage of AS-IV (1 g/kg, qd) at 8 weeks of age and lasted 12 weeks By oral gavage of an equal volume of NS at 8 weeks of age and lasted 12 weeks 1. Renal pathology
2. 24-h urinary protein
3. 24-h urinary NAG and NGAL
4.HbA1c
5.Serum insulin
6.ALT and AST
7.Urinary TGF-β1
8.p-Akt
9.β-actin
10.p-mTOR
11. p-NF-κB
12. p-ERK1/2
13. BG
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05
7. P < 0.05
8. P < 0.05
9. P < 0.05
10. P < 0.05
11 .P < 0.05
12. P < 0.05
13. P < 0.05
Guo et al., 2017 C57BL/6J mice (male, 12/12) NM By intraperitoneal injection of STZ (100 mg/kg, qd) for 2 consecutive days Mice with a blood glucose level over 350 mg/dl after 1 week of STZ injection NM By oral gavage of AS-IV (12 mg/kg, qd) after STZ injection and lasted 8 weeks By oral gavage of an equal volume of NS after STZ injection and lasted 8 weeks 1. Renal pathology
2. BUN and SCr
3. GRP78
4. TF6
5. p-ERK1/2
6. p-eIF2α and p-IRE1α
7. CHOP
8. TRAF2
9. p-JNK
10. Caspase-12
11. SERCA
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05
7. P < 0.05
8. P < 0.05
9. P < 0.05
10. P < 0.05
11. P < 0.05
Liu et al., 2017 db/db mice (male, 6/6) NM C57BL/KSJ mice (Spontaneous diabetes) NM Pentobarbital sodium (75 mg/kg) By oral gavage of AS-IV (1 g/kg, qd) at 8 weeks of age and lasted 12 weeks By oral gavage of an equal volume of NS at 8 weeks of age and lasted 12 weeks 1. Renal pathology
2. 24-h urinary protein
3. 24-h urinary NAG
4. Drp-1, Fis-1, and MFF
5. Mfn-1, Mfn-2,and OPA-1
6. PINK1, Parkin, p-Parkin (Ser 65), and LC-3II
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05
Wang et al., 2017 KKAy mice (male, 10/10) 22–24 g By feeding with high-fat diet for 14 consecutive weeks before experiment and lasted 14 weeks Mice with a blood glucose level over 13.9 mmol/L after 14 weeks of high-fat diet Aether By oral gavage of AS-IV (40 mg/kg, qd) after 14 weeks of high-fat diet and lasted 10 weeks By oral gavage of an equal volume of NS after 14 weeks of high-fat diet and lasted 10 weeks 1. Renal pathology
2. BG
3. α-SMA
4. TGF-β1
5. Smad2/3
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
Du et al., 2018 Wistar rats (male, 8/8) 180–220 g By intraperitoneal injection of STZ (60 mg/kg) Rats with a blood glucose level over 13.8 mg/kg after 72 h of STZ injection NM By oral gavage of AS-IV (16 mg/kg, qd) after STZ injection and lasted 8 weeks By oral gavage of an equal volume of NS after STZ injection and lasted 8 weeks 1. BUN and SCr
2. UCr
3. β2-MG
4. MDA, CAT and GSH-Px
5. T-AOC
1. P< 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
Han et al., 2018 C57BL/6J (male, 6/6) NM By intraperitoneal injection of STZ (200 mg/kg) Mice with a blood glucose level over 16.7 mmol/L NM By oral of feed supplemented with AS-IV (AS-IV:feed = 5g:1kg) and lasted 8 weeks By oral of an equal quality of standard feed and lasted 8 weeks 1.Histological structure of kidney under transmission electron microscopy
2. Renal pathology
3. 24-h urinary protein
4. 24-h urinary NAG and NGAL
5. Kidney/body weight ratio
6. p-Akt
7. p-mTOR
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05
7. P < 0.05
He et al., 2018 SD rats
(male, 10/10)
180–220 g By intraperitoneal injection of STZ (65 mg/kg) Rats with a blood glucose level over 16.7 mmol/L after 72 h of STZ injection NM By oral gavage of AS-IV (10 mg/kg, qd) after STZ injection and lasted 8 weeks By oral gavage of an equal volume of CMC after STZ injection and lasted 8 weeks 1. Renal pathology
2. 24-h urinary protein
3. p-130Cas
1. P < 0.05
2. P < 0.05
3. P < 0.05
Li, 2018 SD rats
(male, 11/10)
180–220 g By intraperitoneal injection of STZ (55 mg/kg) Rats with a blood glucose level over 16.7 mmol/L after 72 h of STZ injection Chloral hydrate (35 mg/kg) By oral gavage of AS-IV (80 mg/kg, qd) after STZ injection and lasted 8 weeks By oral gavage of an equal volume of CMC after STZ injection and lasted 8 weeks 1. Renal pathology
2. 24-h urinary microalbumin
3. Kidney/body weight ratio
4. BUN and SCr
5. BG
6. MDA, SOD, and GSH-Px
7. Nrf2, NQO1, and HO1
8. TGF-β1
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05
7. P < 0.05
8. P < 0.05
Lei et al., 2018a SD rats
(male, 6/6)
200g By intraperitoneal injection of STZ (65 mg/kg) Rats with a blood glucose level over 300 mg/dl after 48 h of STZ injection NM By oral gavage of AS-IV (5 mg/kg, qd) after STZ injection and lasted 12 weeks By oral gavage of an equal volume of citrate buffer after STZ injection and lasted 12 weeks 1. 24-h urinary protein
2. TUG1 level
3. The TRAF5 mRNA and protein level
1. P < 0.05
2. P < 0.05
3. P < 0.05
Lei et al., 2018b SD rats
(male, 6/6)
200–220 g By intraperitoneal injection of STZ (65 mg/kg) Rats with a blood glucose level over 300 mg/dl after 48 h of STZ injection Pentobarbital sodium By oral gavage of AS-IV (5 mg/kg, qd) after STZ injection and lasted 12 weeks By oral gavage of an equal volume of citrate buffer after STZ injection and lasted 12 weeks 1. BUN and SCr
2. TRAF5
3. miR-378
1. P < 0.05
2. P < 0.05
3. P < 0.05
Fan et al., 2019 SD rats
(male, 6/6)
180-200 g By intraperitoneal injection of STZ (65 mg/kg) Rats with a blood glucose level over 300 mg/dl after 48 h of STZ injection pentobarbital sodium By oral gavage of AS-IV (10 mg/kg, qd) after STZ injection and lasted 8 weeks By oral gavage of an equal volume of CMC after STZ injection and lasted 8 weeks 1. Renal pathology
2. HbA1c
3. BUN and SCr
4. Nitric oxide
5. Endothelial nitric oxide synthase
6. Body weight
7. BG
8. 24-h urinary protein
9. Cell apoptosis rate
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05
7. P < 0.05
8. P < 0.05
9. P < 0.05
Ju et al., 2019 SD rats
(male, 8/8)
180–220 g By feeding with high-fat diet for 6 consecutive weeks before modeling+ by intraperitoneal injection of STZ (35 mg/kg) Rats with a blood glucose level over 16.7 mmol/L after 72 h of STZ injection Chloral hydrate By oral gavage of AS-IV (80 mg/kg, qd) in 1 week after STZ injection and lasted 8 weeks By oral gavage of an equal volume of CMC in 1 week after STZ injection and lasted 8 weeks 1. Renal pathology
2. 24-h urinary microalbumin
3. BUN and SCr
4. Kidney/body weight ratio
5. Ratio of urine total protein to UCr
6. CCr
7. BG
8. TG and TC
9. Bax, Bcl-2, and Bax/Bcl-2
10. Caspase-3
11. β-actin
12. GRP78
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05
7. P < 0.05
8. P < 0.05
9. P < 0.05
10. P < 0.05
11. P < 0.05
12. P < 0.05
Liu et al., 2019 SD rats
(male, 10/10)
180-200 g By intraperitoneal injection of STZ (50 mg/kg) Rats with a blood glucose level over 16.7 mmol/L after 72 h of STZ injection NM By oral gavage of AS-IV (60 mg/kg, qd) after STZ injection and lasted 8 weeks By oral gavage of an equal volume of distilled water after STZ injection and lasted 8 weeks 1. BG
2. Urine protein
3. BUN and SCr
4. p-PI3K
5. p-Akt
6. NF-κB
7. Renal hypertrophy index
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05
7. P < 0.05
Ma et al., 2019 SD rats
(male, 13/10)
180–220 g By feeding with high-fat and high-suga diet for 6 consecutive weeks before modeling+ by intraperitoneal injection of STZ (35 mg/kg) Rats with a blood glucose level over 16.7 mmol/L after 72 h of STZ injection Chloral hydrate By oral gavage of AS-IV (80 mg/kg, qd) after STZ injection and lasted 8 weeks By oral gavage of an equal volume of CMC after STZ injection and lasted 8 weeks 1. Renal pathology
2. 24-h urinary microalbumin
3. 24-h urinary protein
4. BUN and SCr
5. Kidney/body weight ratio
6. BG
7. p-Fox O1/Fox O1
8. p-PI3K/PI3K
9. p-Akt/Akt
1. P < 0.05
2. P < 0.05
3. P < 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05
7. P < 0.05
8. P < 0.05
9. P < 0.05
Song et al., 2020 SD rats
(male, 8/8)
200–220 g By intraperitoneal injection of STZ (58 mg/kg) Rats with a blood glucose level over 16.7 mmol/L after 72 h of STZ injection NM By oral gavage of AS-IV (10 mg/kg, qd) after STZ injection and lasted 12 weeks By oral gavage of an equal volume of distilled water after STZ injection and lasted 12 weeks 1. Renal pathology
2. 24-h urinary protein
3. BUN and SCr
4. Kidney/body weight ratio
5. BG
6. Desmin
1. P < 0.05
2. P < 0.05
3. P > 0.05
4. P < 0.05
5. P < 0.05
6. P < 0.05

ALT, alanine aminotransferase; AST, aspartate aminotransferase; BG, blood glucose; BUN, blood urea nitrogen; β2-MG, β2-microglobulin; Cas, crk-associated substrate; CAT, catalase; CCr, creatinine clearance rate; CHOP, CCAAT/enhancer-binding protein homologous protein; CMC, carboxymethyl cellulos; COl-IV, type IV collagen; Cr, creatinine; Drp-1, dynamin-related protein 1; Fis-1, mitochondrial fission protein 1; Fox O1, forkhead box O1; HbA1c, glycated hemoglobin; GRP78, glucose-regulated protein 78; GSH-PX, glutathione peroxidase; HbA1c, glycated hemoglobin; HOMA-IR, homeostatic model assessment of insulin resistance; HDL, high density lipoprotein; ILK, integrin-linked kinase; IL-1β, interleukin-1β; JNK, Jun N-terminal kinases; LDL, low-density lipoprotein; LN, laminin; MCP-1, monocyte chemotactic protein-1; MDA, malondialdehyde; MFF, mitochondrial fission factor; Mfn-1, rabbit antimitofusin 1; Mfn-2, rabbit antimitofusin 2; mTOR, mammalian target of rapamycin; NAG, N-acetyl-β-D-glucosaminidase; NGAL, neutrophil gelatinase-associated lipocalin; NM, not mentioned; NQO1, nad(p)h quinnone dehydrogenase 1; Nrf2, nuclear factor E2 related-factor 2; NS, normal saline; OPA-1, mouse anti-optic atrophy 1; ORP150, 150 kDa oxygen-regulated protein; PERK, PKR-like eukaryotic initiation factor 2A kinase; p-PI3K, phosphorylated phosphatidylinositol-3-kinase; PINK, PTEN-induced putative kinase; SCr, serum creatinine; SD rats, Sprague Dawley rats; SERCA, sarco endoplasmic reticulum calcium adenosine triphosphatase; SOD, superoxide dismutase; STZ, Streptozotocin; T-AOC, total anti-oxidative capacity; TC, Serum total cholesterol; TG, Triglyceride; TP, Total protein; TNF-α, tumor necrosis factor-α; TRAF2, TNF receptor associated factor 2; UCr, urinary creatinine.