Effect of rapamycin on hepatic osteodystrophy in rats with portasystemic shunting

Table 1 Serum and urine biochemistries at 16 wk

	ALP	AST	ALT	Albumin	Testosterone	IGF-I	25-OH vit D	Osteocalcin	u-deoxypyridinoline
	(nkat)	(nkat)	(nkat)	(g/L)	ng/L	μg/L	ng/L	ng/L	(μmol/mol creatinine)
Control	2161 ± 369	1182 ± 277	940 ± 187	16.75 ± 0.71	5.41 ± 2.34	879.37 ± 245.51	25.63 ± 4.04	142.91 ± 32.9	48.8 ± 7.9
Control + rapamycin	2762 ± 389a	2022 ± 1152a	1155 ± 122a	15.78 ± 1.3	10.62 ± 9.1	616.02 ± 189.66	29.15 ± 8.00	147.43 ± 34.0	67.12 ± 13.6
PSS	7144 ± 2121b	2210 ± 741a	1538 ± 243b	15.25 ± 0.75a	3.55 ± 0.41a	290.28 ± 170.90a	23.89 ± 5.97	105.57 ± 38.3a	61.99 ± 18.7
PSS + rapamycin	8481 ± 3380b	3217 ± 1560a	1752 ± 549a	14.33 ± 1.22a	3.45 ± 0.74b	241.66 ± 80.58a	22.15 ± 5.07	119.61 ± 43.5	93.79 ± 30.6a

^aP < 0.05 vs Controls;

^bP < 0.001 vs Controls.

Table 2 Bone analysis at 16 wk

	Whole body BMD mg/cm2	High resolution BMD mg/cm2	Femur length (mm)	Mid-shaft thickness (mm)	Femur mass (g)/kg body mass	Ca2+ mg/g bone	Hyp/g bone
Control (n = 12)	211.7 ± 9	379.7 ± 46	42.8 ± 1.1	4.7 ± 0.3	1.49 ± 0.1	260 ± 7	3576 ± 1980
Control + rapamycin (n = 12)	210.0 ± 8	377.2 ± 43	42.8 ± 1.3	4.7 ± 0.3	1.53 ± 0.1	258 ± 9	6104 ± 1600a
PSS (n = 11)	201.9 ± 8a	309.3 ± 63a	36.6 ± 0.6b	4.1 ± 0.3a	1.80 ± 0.2a	289 ± 5b	2038 ± 878
PSS + Rapamycin (n = 10)	210.5 ± 17	334. ± 64	37.3 ± 1b	3.8 ± 0.3b	1.81 ± 1.37b	297 ± 9b	5489 ± 1250a

^aP < 0.05 vs Controls;

^bP < 0.001 vs Controls.

Table 3 Quantitative histomorphometry

	Osteoid volume, OV/BV (%)	Relative osteoid volume, OV/TV (%)	Osteoid surface, OS/BS (%)	Osteoid thickness, O.Th (μm)	Osteoblast appositional rate, OAR (μm/d)	Mineralization lag time, MLT (d)	Eroded surfaces, ES/BS (%)	Osteoclastic surfaces, OcS/BS (%)
Control	1.26 ± 0.24	0.15 ± 0.04	8.94 ± 1.27	5.67 ± 0.65	1.03 ± 0.09	5.61 ± 1.08	5.63 ± 0.55	1.07 ± 0.20
Control + Rapamycin	1.34 ± 0.38	0.19 ± 0.06	10.44 ± 1.86	5.30 ± 0.93	1.05 ± 0.08	5.06 ± 1.25	6.35 ± 0.81	1.42 ± 0.24
PSS	3.69 ± 1.43	0.66 ± 0.32	17.48 ± 4.96	8.00 ± 1.32	0.85 ± 0.86	19.7 ± 5.07a	3.62 ± 0.63a	0.97 ± 0.28
PSS + Rapamycin	1.33 ± 0.19	0.15 ± 0.02	10.05 ± 1.53	5.72 ± 0.86	0.95 ± 0.11	11.02 ± 1.99	4.40 ± 0.62	0.94 ± 0.19

^aP < 0.05 vs Controls.

Table 4 Cytokine levels, T-lymphocyte subsets and Kupffer cell populations at 16 wk

	IL-1(ng/L)	IL-6(ng/L)	TNFα(ng/L)	%CD3+	%CD4+	%CD8+	Ratio CD4+: CD8+	%CD4+ expressing CD25	%CD8+ expressing CD25	Kupffer cells /10 high power fields
Control	22.28 ± 4.39	0	13.6 ± 2.73	74.05 ± 5.49	43.15 ± 3.93	30.9 ± 7.05	1.4	7.96 ± 2.99d	10.62 ± 2.64f	46.26 ± 7.95
Control + rapamycin	25.86 ± 8.71	0	14.84 ± 2.35	73.34 ± 7.73	47.86 ± 8.31	25.48 ± 6.4	1.8	15.54 ± 9.5d	17.9 ± 13.87f	40.3 ± 8.46
PSS	22.23 ± 5.12	0.025 ± 0.045	26.15 ± 45.97	93.4 ± 7.97a	58.96 ± 9.02	34.47 ± 6.59b	1.6	5.38 ± 2.47c	6.05 ± 1.99e	43.45 ± 8.13
PSS + Rapamycin	26.12 ± 6.21	0.011 ± 0.033	15.5 ± 11.83	73.19 ± 5.66	56.78 ± 5.60	18.39 ± 5.73b	3.1	11.38 ± 6.96c	19.10 ± 14.58e	44.95 ± 9.16

%CD3 + T cells PSS vs controls

^bP < 0.001 vs Controls; %CD8+ T cells PSS vs PSS + Rapamycin

^dP < 0.001; %CD4 + CD25 + T cells PSS vs PSS + Rapamycin

^fP < 0.001; %CD4 + CD25 + T cells Control vs Control + Rapamycin ^hP < 0.001; %CD8 + CD25 + T cells PSS vs PSS + Rapamycin ⁱP < 0.001; %CD8 + CD25 + T cells Control vs Control + Rapamycin ^kP < 0.001.