24 (TUDCA) TUDCA TUDCA. [DOI] /j.issn

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1 [ ] Wistar % 8 24 (TUDCA) (VFW) (FBG) (FINS) (HOMA-IR) (TC) (TG) (SBP) (DBP) N- - -D- (NAG) (m-alb) (BUN) (Scr) VFW FINS HOMA-IR TC TG SBP DBP NAG (P<0.05) m-alb BUN Scr (P>0.05) VFW FINS HOMA-IR TC TG SBP DBP (P<0.05) TUDCA FINS HOMA-IR (P<0.05) TC TG SBP DBP NAG BUN Scr (P>0.05) TUDCA TUDCA [ ] [ ] R587 [ ] A [ ] (2017) [DOI] /j.issn Effects of Coptis chinensis decoction on the metabolic index and renal protection in rats with metabolism syndrome CHEN Xiao-qing 1,2, WANG Qing 1, WANG Li-ping 1,2*, Huang Chun-lai 1, ZHANG Yong 1,2, MA Li-qiang 1,2, YU Yi 1,2, ZHUANG Yong-ze 1,2 1 Department of Nephrology, Fuzhou General Hospital of Nanjing Command, Fuzhou , China 2 Clinical Medical College of Fujian Medical University, Fuzhou , China * Corresponding author, wanglp306@126.com This work was supported by the National Natural Science Foundation of China ( ) [Abstract] Objective To investigate the protective effects of Coptis chinensis decoction on the metabolic index and renal function of rats with fructose-induced metabolism syndrome (MS). Methods From 56 male Wistar rats, 6 were randomly selected as normal control group, the other rats were daily fed with 10% fructose water for 8 weeks to reproduce the MS model. Twenty-four rats were established successfully as MS model and randomly divided into 4 groups (6 each): model group, Coptis decoction group, tauroursodeoxycholic acid (TUDCA) group and berberine hydrochloride (BH) group. The body weight, visceral fat weight, fasting blood glucose (FBG), fasting insulin (FINS), insulin resistance index (HOMA-IR), cholesterol (TC), triglyceride (TG), systolic blood pressure (SBP), diastolic blood pressure (DBP), urinary N-acetyl- -D-glucosidase (NAG), urine microalbumin (m-alb), blood urea nitrogen (BUN) and serum creatinine (Scr) levels were compared between the groups, and the renal pathological changes were observed by light microscopy and electron microscopy. Results The levels of body weight, visceral fat weight, FINS, HOMA- IR, TC, TG, SBP, DBP and urinary NAG were obviously higher in the four MS model groups than in normal control group (P<0.05), while the levels of m-alb, BUN and Scr showed no significant difference (P>0.05). After the intervention, the levels of body weight, [ ] ( ) [ ] [ ] ( ) () [ ] wanglp306@126.com

2 Med J Chin PLA, Vol. 42, No. 11, November 1, visceral fat weight, FINS, HOMA-IR, TC, TG, SBP and DBP decreased significantly in Coptis decoction group than in model group (P<0.05). Compared with BH group and TUDCA group, the levels of FINS and HOMA-IR decreased obviously in Coptis decoction group (P<0.05), while the levels of body weight, TC, TG, SBP, DBP, urinary NAG, BUN and Scr showed no significant difference (P>0.05). It was observed in model group by light microscopy and electron microscopy that the glomerular swelled obviously, the capillary basement membrane of glomerular and renal tubules thickened, mesangial region and interstitial substances hyperplasia, podocytes swelled markedly and most of fusion, the epithelial cells of renal tubules serious vacuolar degeneration, and a lot of secondary lysosomes formed, autophagy of organelles occurred, and most of endoplasmic reticulum and mitochondria disappeared. The kidney pathological damage reduced obviously after treatment of Coptis decoction, but no significant difference when compared with that in BH group and TUDCA group. Conclusions Coptis decoction may decrease the body weight, reduce the levels of blood lipid and blood pressure, and better improve the insulin resistance when compared with BH and TUDCA. In addition, Coptis decoction can also reduce the renal pathological damage, and has the protective function for kidney. [Key words] Coptis decoction; metabolic syndrome; kidney; insulin resistance (metabolic syndrome MS) ( ) (IR) [1] MS 11% [2] MS (chronic kidney disease CKD) MS CKD CKD [3] MS MS MS Wistar ~180g SCXK( ) %~60% 20~ ( ) 300g 30min ml 0.5g/ml (berberine PHR 1502)500mg (tauroursodeoxycholic acid TUDCA T0266-1G) (fructose PHR-1G) Sigma 1.3 MS % 8 (FBG) (FINS) (HOMA-IR) HOMA-IR 2 MS 24 TUDCA 4 6 1g/(kg d) 100mg/(kg d) TUDCA 100mg/(kg d) % FBG (BUN) (Scr) FINS 8 12h 1% (100mg/kg) 80 Olympus AU2700 FBG BUN Scr FINS HOMA-IR (HOMA) HOMA-IR HOMA-IR= / (m-alb) 8 24h 24h 5ml 3500r/min 5min 80 m-alb N- - -D- (N-acetyl- -D-glucosa minidase NAG) N- - -D 1.4.5

3 ~15min (VFC) VFC VFC= (VFW)/ 100% % 24h HE PAS 1mm 3 2~3 1.5 SPSS 17.0 x±s t LSD-t P< VFW (P<0.01) 8 TUDCA (P>0.05) VFW (P<0.01) 8 VFW (P<0.01) TUDCA VFW VFW TUDCA ( P <0.05) (P>0.05 1) 2.3 FBG FINS HOMA-IR FINS HOMA-IR (P<0.05) 8 FINS HOMA-IR (P<0.01) TUDCA FINS (P<0.05) HOMA-IR (P>0.05) FBG (P>0.05 2) 2.4 TC TG SBP DBP 1 16 VFW (g x±s n=6) Tab.1 Comparison of body weight and VFW at the 16th week between the groups (g, x±s, n=6) Group Body weight VFW Control group Model group (1) (1) Coptis decoction group (1)(2) (3) Berberine group (1)(2) (3) TUDCA group (1)(3) (1)(4)(5) VFW. Visceral fat weight; TUDCA. Tauroursodeoxycholic acid; (1)P<0.01 compared with control group; (2)P<0.05, (3)P<0.01 compared with model group; (4)P<0.01 compared with Coptis decoction group; (5)P<0.05 compared with berberine group 2 FBG FINS HOMA-IR (x±s n=6) Tab.2 Comparison of FBG, FINS and HOMA-IR between the groups (x±s, n=6) Group FBG(mmol/L) FINS( U/ml) HOMA-IR Control group Model group (2) (2) Coptis decoction group (1)(4) (2)(4) Berberine group (2)(3)(6) (2)(6) TUDCA group (2)(4)(5) (2)(5) FBG. Fasting blood glucose; FINS. Fasting insulin; HOMA- IR. Insulin resistance index; TUDCA. Tauroursodeoxycholic acid; (1)P<0.05, (2)P<0.01 compared with control group; (3)P<0.05, (4)P<0.01 compared with model group; (5)P<0.05, (6)P<0.01 compared with Coptis decoction group (P<0.05) 8 TC TG SBP DBP (P<0.05) (P>0.05 3) 2.5 NAG m-alb Scr BUN NAG (P<0.01) NAG (P>0.05) m-alb Scr BUN (P>0.05 4) TUDCA ( 1) 2.6.2

4 Med J Chin PLA, Vol. 42, No. 11, November 1, (x±s n=6) Tab.3 Comparison of blood lipids and blood pressure between the groups (x±s, n=6) Group TC (mmol/l) TG (mmol/l) SBP (mmhg) DBP (mmhg) Control group Model group (2) (1) (2) (2) Coptis decoction group (2)(3) (1)(3) (2)(4) (2)(4) Berberine group (2)(4) (1)(3) (2)(4) (2)(4) TUDCA group (2)(4) (1)(3) (2)(4) (2)(3) TC. Cholesterol; TG. Triglyceride; SBP. Systolic blood pressure; DBP. Diastolic blood pressure; TUDCA. Tauroursodeoxycholic acid; (1)P<0.05, (2)P<0.01 compared with control group; (3)P<0.05, (4)P<0.01 compared with model group 4 NAG m-alb Scr BUN (x±s n=6) Tab.4 Comparison of urine NAG, urine m-alb, Scr and BUN between the groups (x±s, n=6) Group Urine NAG (U/L) Urine m-alb (mg/l) Scr ( mol/l) BUN (mmol/l) Control group Model group (1) Coptis decoction group (1) Berberine group (1)(2) TUDCA group (1)(3) NAG. N-acetyl- -D-glucosidase; m-alb. Microalbumin; BUN. Blood urea nitrogen; Scr. Serum creatinine; TUDAC. Tauroursodeoxycholic acid; (1)P<0.01 compared with control group; (2)P<0.05 compared with Coptis decoction group; (3)P<0.01 compared with berberine group A B C D E 1 (PAS 100) Fig. 1 Renal pathological performance in each group (PAS 100) A. Control group; B. Model group; C. Coptis decoction group; D. Berberine group; E. Tauroursodeoxycholic acid (TUDCA) group TUDCA ( 2) 3 MS [4] MS CKD [5-6] MS CKD MS CKD MS CKD (14.8%) (8.3%) [7] [8] 150 MS 100 MS MS MS ( ) ( ) - ( ) ( ) MS CKD [9] CKD MS( [10-13] )

5 Glomerutus Renal tubules Control group Model group Coptis decoction group Berberine group TUDCA group 2 ( ) Fig. 2 Ultrastructure of rat kidneys in each group (Transmission electron microscope ) MS MS NAG [14] NAG MS MS MS 2 MS [15-17] MS 78(GRP78) CIEBP (CHOP) mrna MS [18] TUDCA TUDCA TUDCA MS TG TC MS [1] Chinese Diabetes Society. Updated key points of 2013 China

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